Nils Tore Vethe

• Lauritzen, Trine; Munkhaugen, John; Bergan, Stein; Peersen, Kari; Svarstad, Anja Camilla & Andersen, Anders Mikal [Show all 9 contributors for this article] (2024). The atorvastatin metabolite pattern in muscle tissue and blood plasma is associated with statin muscle side effects in patients with coronary heart disease; An exploratory case-control study. Atherosclerosis Plus. ISSN 2667-0909. 55, p. 31–38. doi: 10.1016/j.athplu.2024.01.001. Full text in Research Archive Show summary

  Background and aims Statin-associated muscle symptoms (SAMS) is a prevalent cause of statin discontinuation. It is challenging and time-consuming for clinicians to assess whether symptoms are caused by the statin or not, and diagnostic biomarkers are requested. Atorvastatin metabolites have been associated with SAMS. We aimed to compare atorvastatin pharmacokinetics between coronary heart disease (CHD) patients with and without clinically statin intolerance and statin-dependent histopathological alterations in muscle tissue. Secondarily we aimed to assess genetic variants relevant for the observed pharmacokinetic variables. Methods Twenty-eight patients with CHD and subjective SAMS were included in the exploratory MUSE biomarker study in 2020. Participants received atorvastatin 40 mg/day for seven weeks followed by no statins for eight weeks. Muscle biopsies and blood were collected at the end of each period. Four patients were categorized as clinically intolerant to ≥3 statins prior to study start whereas four patients had signs of muscle cell damage during treatment. Results We found significantly lower levels of atorvastatin acids, and higher lactone/acid ratios in the statin intolerant, both in muscle and plasma. With optimal cut-off, the combination of 2-OH-atorvastatin acid and the 2-OH-atorvastatin lactone/acid ratio provided sensitivity, specificity, and predictive values of 100 %. Patients with variants in UGT1A1 and UGT1A3 had higher lactone metabolite levels than those with wild type, both in muscle and plasma. Conclusion Atorvastatin metabolites appear promising as biomarkers for the identification of clinical statin intolerance in patients with self-perceive

• Pivoriunas, Jonas; Vethe, Nils Tore; Husebye, Einar; Fagerland, Morten; Bergan, Stein & Kristiansen, Oscar [Show all 8 contributors for this article] (2024). Validation of a novel direct method to determine reduced adherence to atorvastatin therapy. European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. doi: 10.1093/ehjcvp/pvae001. Show summary

  Aims Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut‐off values based on the sum of atorvastatin and its major metabolites in blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values. Methods and results The pharmacokinetic study included 60 participants treated with atorvastatin 20 mg (N=20), 40 mg (N=20), and 80 mg (N=20). Atorvastatin was then stopped and blood samples collected from day zero to day four. Quantification of the parent drug and its metabolites in blood plasma was performed with a liquid chromatography-tandem mass spectrometry assay. The cut-off values for reduced adherence were validated and optimized by calculating diagnostic sensitivity and specificity. Our candidate cut-off value of dose-normalized six-component sum of atorvastatin plus metabolites <0.10 nM/mg provided a sensitivity of 97% and a specificity of 93% for detecting ≥2 omitted doses. An optimized cut-off <0.062 nM/mg provided a sensitivity of 90% and a specificity of 100%. An alternative simplified two-component metabolite sum with cut-off value <0.05 nM/mg provided a sensitivity of 98% and a specificity of 76%. An optimized cut-off <0.02 nM/mg provided a sensitivity of 97% and a specificity of 98%. Conclusion This validation study confirms that our direct method discriminates reduced adherence from adherence to atorvastatin therapy with high diagnostic accuracy. The method may improve lipid management in clinical practice and serve as a useful tool in future studies.

• Vethe, Nils Tore; Åsberg, Anders; Andersen, Anders Mikal; Skauby, Ragnhild Kristine Heier; Bergan, Stein & Midtvedt, Karsten (2023). Clinical performance of volumetric finger-prick sampling for the monitoring of tacrolimus, creatinine and haemoglobin in kidney transplant recipients. British Journal of Clinical Pharmacology. ISSN 0306-5251. 89(12), p. 3690–3701. doi: 10.1111/bcp.15870. Full text in Research Archive
• Sverre, Elise Christine Bjørkholen; Munkhaugen, John; Kristiansen, Oscar; Weedon-Fekjær, Harald; Peersen, Kari & Gjertsen, Erik [Show all 10 contributors for this article] (2023). Plasma concentration of atorvastatin metabolites correlates with low-density lipoprotein cholesterol reduction in patients with coronary heart disease. Pharmacology Research & Perspectives. ISSN 2052-1707. 11(3). doi: 10.1002/prp2.1089. Full text in Research Archive Show summary

  In this exploratory study from a randomized double-blinded crossover trial including 70 patients with coronary heart disease and self-perceived muscular side effects of statins, we aimed to determine the relationship between low-density lipoprotein cholesterol (LDL-C) reduction and atorvastatin metabolite plasma concentrations. All patients underwent a 7 weeks treatment period with atorvastatin 40 mg/day and a 7 weeks placebo period in random order. Nonlinear regression with a three-parameter equation explored the relationship between percentage LDL-C reduction (statin vs. placebo) and the pharmacokinetic variables. Mean LDL-C reduction was 49% (range 12% to 71%). The sum of 4-OH-atorvastatin acid and lactone correlated moderately with the LDL-C response (Spearman ρ 0.27, 95% confidence interval [CI]: 0.03 to 0.48). Accordingly, nonlinear regression showed R2 of 0.14 (95% CI: 0.03 to 0.37, R2 adjusted equaled 0.11). Even a perfect underlying correlation of 1.0 showed R2 = 0.32 by simulation, using historical intra-individual LDL-C variation (8.5%). The 90% inhibitory concentration was 2.1 nmol/L, and the 4-OH-metabolite sum exceeded this threshold in 34% of the patients. In conclusion, trough plasma concentrations of 4-OH-atorvastatin metabolites correlated moderately to the LDL-C reduction. A plateau LDL-C response was observed above a pharmacokinetic threshold, below which the response was highly variable. The usefulness of monitoring concentrations of atorvastatin metabolites to optimize the individual dosage have limitations, but its supportive potential may be pursued in relevant patient subsets to achieve adequate efficacy at the lowest possible dose. The results add knowledge to the overall understanding of the variable LDL-C response mediated by atorvastatin.

• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen & Nebauer, Shane Desmond [Show all 13 contributors for this article] (2023). Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin-Associated Muscle Symptoms. Clinical Pharmacology and Therapeutics. ISSN 0009-9236. 113(4), p. 887–895. doi: 10.1002/cpt.2844. Full text in Research Archive Show summary

  Self-perceived statin-associated muscle symptoms (SAMS) are prevalent, but only a minority is drug-dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self-perceived SAMS during 7 weeks of double-blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non-SAMS) attended the present follow-up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non-SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.

• Vethe, Nils Tore; Husebye, Einar; Andersen, Anders Mikal; Bergan, Stein; Kristiansen, Oskar & Fagerland, Morten [Show all 7 contributors for this article] (2022). Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma. Therapeutic Drug Monitoring. ISSN 0163-4356. 44(4), p. 558–567. doi: 10.1097/FTD.0000000000000992. Show summary

  Background:  Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD). Methods:  Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography–tandem mass spectrometry. Results:  A simvastatin acid cutoff of 1.0 × 10−2 nmol−1·L−1·mg−1 identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range −2.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 × 10−3 nmol−1·L−1·mg−1. Conclusions:  The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged.

• Sverre, Elise Christine Bjørkholen; Peersen, Kari; Kristiansen, Oscar; Fagerland, Morten; Perk, Joep & Husebye, Einar [Show all 9 contributors for this article] (2022). Tailored clinical management after blinded statin challenge improved the lipid control in coronary patients with self-perceived muscle side effects. Journal of Internal Medicine. ISSN 0954-6820. 291(6), p. 891–893. doi: 10.1111/joim.13454.
• Peersen, Kari; Munkhaugen, John; Sverre, Elise Christine Bjørkholen; Kristiansen, Oskar; Fagerland, Morten & Vethe, Nils Tore [Show all 9 contributors for this article] (2021). Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects. BMC Cardiovascular Disorders. ISSN 1471-2261. 21, p. 1–9. doi: 10.1186/s12872-021-02422-7. Full text in Research Archive Show summary

  Background: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). Methods: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. Results: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. Conclusions: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

• Kristiansen, Oskar; Sverre, Elise Christine Bjørkholen; Peersen, Kari; Fagerland, Morten; Gjertsen, Erik & Gullestad, Lars [Show all 11 contributors for this article] (2021). The relationship between directly measured statin adherence, self-reported adherence measures and cholesterol levels in patients with coronary heart disease. Atherosclerosis. ISSN 0021-9150. 336, p. 23–29. doi: 10.1016/j.atherosclerosis.2021.09.020. Full text in Research Archive Show summary

  Background and aims: We aimed to determine the relationship between statin adherence measured directly, and by self-report measures and serum cholesterol levels. Methods: Patients prescribed atorvastatin (N = 373) participated in a cross-sectional study 2–36 months after a coronary event. Self-reported adherence included statin adherence the past week, the 8-item Morisky medication adherence scale (MMAS-8), and the Gehi et al. adherence question. Atorvastatin was measured directly in spot blood plasma by a novel liquid chromatography tandem mass-spectrometry method discriminating adherence (0–1 doses omitted) and reduced adherence (≥2 doses omitted). Participants were unaware of the atorvastatin analyses at study participation. Results: Mean age was 63 (SD 9) years and 8% had reduced atorvastatin adherence according to the direct method. In patients classified with reduced adherence by the direct method, 40% reported reduced statin adherence, 32% reported reduced adherence with the MMAS-8 and 22% with the Gehi question. In those adherent by the direct method, 96% also reported high statin adherence, 95% reported high adherence on the MMAS-8 whereas 94% reported high adherence on the Gehi question. Cohen’s kappa agreement score with the direct method was 0.4 for self-reported statin adherence, 0.3 for the Gehi question and 0.2 for the MMAS-8. Adherence determined by the direct method, self-reported statin adherence last week, and the Gehi question was inversely related to LDL-cholesterol levels with a p-value of <0.001, 0.001 and 0.004, respectively. Conclusions: Plasma-statin measurements reveal reduced adherence with higher sensitivity than self-report measures, relate to cholesterol levels, and may prove to be a useful tool to improve lipid management.

• Skauby, Ragnhild Kristine Heier; Bergan, Stein; Andersen, Anders Mikal; Vethe, Nils Tore & Christensen, Hege (2021). In vitro assessments predict that CYP3A4 contributes to a greater extent than CYP3A5 to prednisolone clearance. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 129(6), p. 427–436. doi: 10.1111/bcpt.13645. Show summary

  Because several steroid hormones are metabolized to their respective 6β-hydroxy forms by CYP3A4 and CYP3A5, these isoenzymes have been assumed to metabolize the immunosuppressive drug prednisolone, with conflicting results in the literature with respect to their relative importance. A direct study of the metabolism of prednisolone by microsomal CYP3A4 and CYP3A5 is missing. The aim of this in vitro study was to investigate the relative importance of recombinant CYP3A4 and recombinant CYP3A5 in the metabolism of prednisolone and to compare the extent of formation of 6β-OH-prednisolone by the two enzymes. Through in vitro incubations using rCYP3A4 and rCYP3A5 enzymes, intrinsic clearance (CLint) of prednisolone was determined by the substrate depletion approach. Formation of the metabolite 6β-OH-prednisolone by rCYP3A4 and rCYP3A5, respectively, was compared. Prednisolone concentrations were measured, and its metabolite 6β-OH-prednisolone was identified using a HPLC-MS/MS in-house method. CLint for prednisolone by rCYP3A5 was less than 26% relative to rCYP3A4. Formation of 6β-OH-prednisolone by rCYP3A5 was less than 11% relative to rCYP3A4. The study indicates that 6β-hydroxylation of prednisolone assessed in vitro in recombinant CYP enzymes depends on rCYP3A4 rather than rCYP3A5 and that CYP3A5 may be responsible for the formation of other prednisolone metabolite(s) in addition to 6β-OH-prednisolone.

• Andersen, Anders Mikal; Bergan, Stein; Gedde-Dahl, Tobias; Buechner, Jochen & Vethe, Nils Tore (2021). Fast and reliable quantification of busulfan in blood plasma using two-channel liquid chromatography tandem mass spectrometry: Validation of assay performance in the presence of drug formulation excipients. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 203, p. 1–11. doi: 10.1016/j.jpba.2021.114216. Full text in Research Archive
• Kindem, Ingvild Andrea; Bjerre, Anna Kristina; Åsberg, Anders; Midtvedt, Karsten; Bergan, Stein & Vethe, Nils Tore (2021). Tacrolimus Measured in Capillary Volumetric Microsamples in Pediatric Patients—A Cross-Validation Study. Therapeutic Drug Monitoring. ISSN 0163-4356. 43(3), p. 371–375. doi: 10.1097/FTD.0000000000000873. Full text in Research Archive
• Bergan, Stein; Brunet, Mercé; Hesselink, Dennis A.; Johnson-Davis, Kamisha L; Kunicki, Pawel K & Lemaitre, Florian [Show all 38 contributors for this article] (2021). Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Therapeutic Drug Monitoring. ISSN 0163-4356. 43(2), p. 150–200. doi: 10.1097/FTD.0000000000000871.
• Klaasen, Rolf; Bergan, Stein; Bremer, Sara; Hole, Kristine; Nordahl, Christine Berg & Andersen, Anders Mikal [Show all 9 contributors for this article] (2020). Pharmacodynamic assessment of mycophenolic acid in resting and activated target cell population during the first year after renal transplantation. British Journal of Clinical Pharmacology. ISSN 0306-5251. 86(6), p. 1100–1112. doi: 10.1111/bcp.14218.
• Skauby, Ragnhild Kristine Heier; Gustavsen, Marte Theie; Andersen, Anders Mikal; Bjerre, Anna Kristina; Åsberg, Anders & Midtvedt, Karsten [Show all 8 contributors for this article] (2020). Prednisolone and Prednisone Pharmacokinetics in Adult Renal Transplant Recipients. Therapeutic Drug Monitoring. ISSN 0163-4356. 43(2), p. 247–255. doi: 10.1097/FTD.0000000000000835.
• Amrutkar, Manoj; Vethe, Nils Tore; Verbeke, Caroline Sophie; Aasrum, Monica; Vefferstad, Anette & Santha, Petra [Show all 7 contributors for this article] (2020). Differential gemcitabine sensitivity in primary human pancreatic cancer cells and paired stellate cells is driven by heterogenous drug uptake and processing. Cancers. ISSN 2072-6694. 12:3628(12), p. 1–18. doi: 10.3390/cancers12123628. Full text in Research Archive
• Gustavsen, Marte Theie; Midtvedt, Karsten; Robertsen, Ida; Woillard, Jean-Baptiste; Debord, Jean & Klaasen, Rolf [Show all 9 contributors for this article] (2020). Fasting Status and Circadian Variation Must be Considered When Performing AUC-based Therapeutic Drug Monitoring of Tacrolimus in Renal Transplant Recipients. Clinical and Translational Science (CTS). ISSN 1752-8054. 13(6), p. 1327–1335. doi: 10.1111/cts.12833.
• Kvamsøe, Marianne Meling; Hansen, Kristina Ravnås; Skadberg, Øyvind; Vethe, Nils Tore & Brede, Cato (2020). Salting Out-Assisted Liquid–Liquid Extraction for Liquid Chromatography–Tandem Mass Spectrometry Measurement of Tacrolimus, Sirolimus, Everolimus, and Cyclosporine a in Whole Blood. Therapeutic Drug Monitoring. ISSN 0163-4356. 42(5), p. 695–701. doi: 10.1097/FTD.0000000000000794. Show summary

  Background: Therapeutic drug monitoring of the immunosuppressants tacrolimus, sirolimus, everolimus, and cyclosporine A is effectively performed by analyzing whole-blood samples using liquid chromatography coupled with tandem mass spectrometry. Samples are usually prepared using simple protein precipitation (PPT) with methanol and zinc sulfate (ZnSO4). Significant sample dilution is necessary to obtain clean extracts but may increase the limit of quantification of the method. Salting out–assisted liquid–liquid extraction (SALLE) was explored as a novel sample preparation method for measuring these drugs in blood. Method: SALLE, which simply consists of LLE with a water-miscible solvent where phase separation is achieved by adding salt, was used to analyze treated blood samples. Results: SALLE allowed direct injection of a 5-µL extract from the upper solvent phase into a reversed phase LC column, which would not be feasible using standard LLE. Compared with PPT, SALLE provided better extraction efficiencies and more ion enhancement, resulting in limit of quantification of 0.4, 1.4, 0.06, and 0.4 ng/mL for tacrolimus, sirolimus, everolimus, and cyclosporine A, respectively. Full-method validation was performed, including a comparison of results with those of another laboratory. A ≤10% bias was observed for tacrolimus and cyclosporine A, whereas further investigation of that for sirolimus (−12%) and everolimus (−18%) revealed that it was caused by the different calibrators used. Conclusions: This is the first report of the use of SALLE for the measurement of tacrolimus, sirolimus, everolimus, and cyclosporine A in whole blood. The advantages of SALLE over PPT and conventional LLE would make it an attractive sample preparation method for clinical laboratories.

• Lemaitre, Florian; Vethe, Nils Tore; DʼAvolio, Antonio; Tron, Camille; Robertsen, Ida & De Winter, Brenda [Show all 14 contributors for this article] (2020). Measuring intracellular concentrations of calcineurin inhibitors: Expert consensus from the international association of therapeutic drug monitoring and clinical toxicology expert panel. Therapeutic Drug Monitoring. ISSN 0163-4356. 42(5), p. 665–670. doi: 10.1097/FTD.0000000000000780.
• Kristiansen, Oskar; Vethe, Nils Tore; Peersen, Kari; Fagerland, Morten; Sverre, Elise Christine Bjørkholen & Jensen, Elena Prunès [Show all 15 contributors for this article] (2020). Effect of Atorvastatin on Muscle Symptoms in Coronary Heart Disease Patients With Self-Perceived Statin Muscle Side-Effects: A Randomized, Double Blinded Crossover Trial . European Heart Journal (EHJ) - Cardiovascular Pharmacotherapy. ISSN 2055-6837. 7(6), p. 507–516. doi: 10.1093/ehjcvp/pvaa076. Full text in Research Archive
• Gustavsen, Marte Theie; Midtvedt, Karsten; Vethe, Nils Tore; Robertsen, Ida; Bergan, Stein & Åsberg, Anders (2020). Tacrolimus area under the concentration versus time curve monitoring, using home-based volumetric absorptive capillary microsampling. Therapeutic Drug Monitoring. ISSN 0163-4356. 42(3), p. 407–414. doi: 10.1097/FTD.0000000000000697.
• Bergström, Marcus; Müller, Malin; Karlsson, Marie; Scholz, Hanne; Vethe, Nils Tore & Korsgren, Olle (2019). Comparing the Effects of the mTOR Inhibitors Azithromycin and Rapamycin on In Vitro Expanded Regulatory T Cells . Cell Transplantation. ISSN 0963-6897. 28(12), p. 1603–1613. doi: 10.1177/0963689719872488. Full text in Research Archive
• Kristiansen, Oscar; Vethe, Nils Tore; Fagerland, Morten; Bergan, Stein; Munkhaugen, John & Husebye, Einar (2019). A novel direct method to determine adherence to atorvastatin therapy in patients with coronary heart disease. British Journal of Clinical Pharmacology. ISSN 0306-5251. p. 1–8. doi: 10.1111/bcp.14122. Full text in Research Archive
• Vethe, Nils Tore; Gustavsen, Marte Theie; Midtvedt, Karsten; Lauritsen, May Ellen; Andersen, Anders Mikal & Åsberg, Anders [Show all 7 contributors for this article] (2019). Tacrolimus Can Be Reliably Measured With Volumetric Absorptive Capillary Microsampling Throughout the Dose Interval in Renal Transplant Recipients. Therapeutic Drug Monitoring. ISSN 0163-4356. 41(5), p. 607–614. doi: 10.1097/FTD.0000000000000655.
• Brunet, Mercé; van Gelder, Teun; Åsberg, Anders; Haufroid, Vincent; Hesselink, Dennis A. & Langman, Loralie [Show all 37 contributors for this article] (2019). Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy: Second Consensus Report. Therapeutic Drug Monitoring. ISSN 0163-4356. 41(3), p. 261–307. doi: 10.1097/FTD.0000000000000640.
• Munkhaugen, John; Vethe, Nils Tore; Fagerland, Morten; Dammen, Toril; Perk, Joep & Gjertsen, Erik [Show all 10 contributors for this article] (2019). Statin-associated muscle symptoms in coronary patients: design of a randomized study. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 53(3), p. 162–168. doi: 10.1080/14017431.2019.1612085. Full text in Research Archive
• Vethe, Nils Tore; Munkhaugen, John; Andersen, Anders Mikal; Husebye, Einar & Bergan, Stein (2019). A Method for Direct Monitoring of Atorvastatin Adherence in Cardiovascular Disease Prevention: Quantification of the Total Exposure to Parent Drug and Major Metabolites Using 2-Channel Chromatography and Tandem Mass Spectrometry. Therapeutic Drug Monitoring. ISSN 0163-4356. 41(1), p. 19–28. doi: 10.1097/FTD.0000000000000578. Full text in Research Archive
• Klaasen, Rolf; Egeland, Erlend Johannessen; Chan, Wai Joe; Midtvedt, Karsten; Svensson, My Hanna Sofia & Bolstad, Nils [Show all 12 contributors for this article] (2019). A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. Therapeutic Drug Monitoring. ISSN 0163-4356. 41(1), p. 11–18. doi: 10.1097/FTD.0000000000000580.
• Munkhaugen, John; Ruddox, Vidar; Halvorsen, Sigrun; Dammen, Toril; Fagerland, Morten & Hernæs, Kjersti Helene [Show all 23 contributors for this article] (2019). BEtablocker Treatment After acute Myocardial Infarction in revascularized patients without reduced left ventricular ejection fraction (BETAMI): Rationale and design of a prospective, randomized, open, blinded end-point study. American Heart Journal. ISSN 0002-8703. 208, p. 37–46. doi: 10.1016/j.ahj.2018.10.005. Full text in Research Archive
• Klaasen, Rolf; Bergan, Stein; Bremer, Sara; Daleq, Lina; Andersen, Anders Mikal & Midtvedt, Karsten [Show all 8 contributors for this article] (2018). Longitudinal Study of Tacrolimus in Lymphocytes During the First Year After Kidney Transplantation. Therapeutic Drug Monitoring. ISSN 0163-4356. doi: 10.1097/FTD.0000000000000539.
• Krogstad, Veronica; Vethe, Nils Tore; Robertsen, Ida; Hasvold, Grete; Ose, Anne-Marthe Due & Hermann, Monica [Show all 12 contributors for this article] (2018). Determination of Tacrolimus Concentration and Protein Expression of P-Glycoprotein in Single Human Renal Core Biopsies. Therapeutic Drug Monitoring. ISSN 0163-4356. 40(3), p. 292–300. doi: 10.1097/FTD.0000000000000510.
• Skauby, Ragnhild Kristine Heier; Bjerre, Anna Kristina; Sæves, Ingjerd; Vethe, Nils Tore; Bremer, Sara & Svarstad, Anja Camilla [Show all 7 contributors for this article] (2017). Prednisolone and Prednisone Pharmacokinetics in Pediatric Renal Transplant Recipients - A Prospective Study. Therapeutic Drug Monitoring. ISSN 0163-4356. 39(5), p. 472–482. doi: 10.1097/FTD.0000000000000439.
• Bremer, Sara; Vethe, Nils Tore; Skauby, Morten Heier; Kasbo, Margrete; Johansson, Elisabet Dahl & Midtvedt, Karsten [Show all 7 contributors for this article] (2017). NFAT-regulated cytokine gene expression during tacrolimus therapy early after renal transplantation. British Journal of Clinical Pharmacology. ISSN 0306-5251. 83(11), p. 2494–2502. doi: 10.1111/bcp.13367.
• Kloster-Jensen, Kristine; Sahraoui, Afaf; Vethe, Nils Tore; Korsgren, Olle; Bergan, Stein & Foss, Aksel [Show all 7 contributors for this article] (2016). Treatment with tacrolimus and sirolimus reveals no additional adverse effects on human islets in vitro compared to each drug alone but they are reduced by adding glucocorticoids. Journal of Diabetes Research. ISSN 2314-6745. 2016. doi: 10.1155/2016/4196460. Full text in Research Archive Show summary

  Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 μg/L), sirolimus (30 μg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 μg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus.

• Bergan, Stein; Bremer, Sara & Vethe, Nils Tore (2016). Drug target molecules to guide immunosuppression. Clinical Biochemistry. ISSN 0009-9120. 49(4-5), p. 411–418. doi: 10.1016/j.clinbiochem.2015.10.001.
• Kloster-Jensen, Kristine; Vethe, Nils Tore; Bremer, Sara; Abadpour, Shadab; Korsgren, Olle & Foss, Aksel [Show all 8 contributors for this article] (2015). Intracellular sirolimus concentration is reduced by tacrolimus in human pancreatic islets in vitro. Transplant International. ISSN 0934-0874. 28(10), p. 1152–1161. doi: 10.1111/tri.12617.
• Robertsen, Ida; Vethe, Nils Tore; Midtvedt, Karsten; Falck, Pål; Christensen, Hege Staaland & Åsberg, Anders (2015). Closer to the site of action: everolimus concentrations in peripheral blood mononuclear cells correlate well with whole blood concentrations. Therapeutic Drug Monitoring. ISSN 0163-4356. 37(5), p. 675–680. doi: 10.1097/FTD.0000000000000185.
• Robertsen, Ida; Åsberg, Anders; Ingerø Olsen, Aleksander; Vethe, Nils Tore; Bremer, Sara & Bergan, Stein [Show all 7 contributors for this article] (2015). Use of generic tacrolimus in elderly renal transplant recipients: Precaution is needed. Transplantation. ISSN 0041-1337. 99(3), p. 528–532. doi: 10.1097/TP.0000000000000384.
• Vethe, Nils Tore; Ali, Mohamad; Reine, Pål Aarstrand; Andersen, Anders Mikal; Bremer, Sara & Line, Pål Dag [Show all 8 contributors for this article] (2014). Simultaneous Quantification of IMPDH Activity and Purine Bases in Lymphocytes Using LC-MS/MS: Assessment of Biomarker Responses to Mycophenolic Acid . Therapeutic Drug Monitoring. ISSN 0163-4356. 36, p. 108–118. doi: 10.1097/FTD.0b013e3182a13900.
• Sæves, Ingjerd; Line, Pål Dag; Bremer, Sara; Vethe, Nils Tore; Tveit, Ragnhild G & Meltevik, Tore J [Show all 7 contributors for this article] (2014). Tacrolimus exposure and mycophenolate pharmacokinetics and pharmacodynamics early after liver transplantation. Therapeutic Drug Monitoring. ISSN 0163-4356. 36(1), p. 46–53. doi: 10.1097/FTD.0b013e31829dcb66.
• Robertsen, Ida; Åsberg, Anders; Granseth, Tone; Vethe, Nils Tore; Akhlaghi, Fatemeh & Ghareeb, Mwlod [Show all 10 contributors for this article] (2014). More potent lipid-lowering effect by rosuvastatin compared with fluvastatin in everolimus-treated renal transplant recipients. Transplantation. ISSN 0041-1337. 97(12), p. 1266–1272. doi: 10.1097/01.TP.0000443225.66960.7e.
• Reine, Pål Aarstrand; Vethe, Nils Tore; Kongsgaard, Ulf; Andersen, Anders Mikal; Line, Pål Dag & Ali, Mohamad [Show all 7 contributors for this article] (2013). Mycophenolate pharmacokinetics and inosine monophosphate dehydrogenase activity in liver transplant recipients with an emphasis on therapeutic drug monitoring. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 73(2), p. 117–124. doi: 10.3109/00365513.2012.745947.
• Fagermoen, Frode Even; Sulheim, Dag; Winger, Anette; Andersen, Anders Mikal; Vethe, Nils Tore & Saul, J P [Show all 8 contributors for this article] (2012). Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial. BMC Research Notes. ISSN 1756-0500. 5. doi: 10.1186/1756-0500-5-418. Full text in Research Archive
• Sæves, Ingjerd; Vethe, Nils Tore & Bergan, Stein (2011). Quantification of 6 Glucocorticoids in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Method Development, Validation, and Assessment of Matrix Effects. Therapeutic Drug Monitoring. ISSN 0163-4356. 33(4), p. 402–410. doi: 10.1097/FTD.0b013e3182241799.
• Midtvedt, Karsten; Jenssen, Trond Geir; Hartmann, Anders; Vethe, Nils Tore; Bergan, Stein & Havnes, Kjerstin [Show all 7 contributors for this article] (2011). No change in insulin sensitivity in renal transplant recipients converted from standard to once-daily prolonged release tacrolimus. Nephrology, Dialysis and Transplantation. ISSN 0931-0509. 26(11), p. 3767–3772. doi: 10.1093/ndt/gfr153.
• Vethe, Nils Tore; Midtvedt, Karsten; Åsberg, Anders; Amundsen, Rune & Bergan, Stein (2011). Legemiddelinteraksjoner og immunsuppresjon hos organtransplanterte. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 131(20), p. 2000–2003. doi: 10.4045/tidsskr.11.0138.
• Vethe, Nils Tore; Gjerdalen, LC & Bergan, Stein (2010). Determination of cyclosporine, tacrolimus, sirolimus and everolimus by liquid chromatography coupled to electrospray ionization and tandem mass spectrometry: Assessment of matrix effects and assay performance. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 70(8), p. 583–591. doi: 10.3109/00365513.2010.531141.
• Amundsen, Rune; Åsberg, Anders; Robertsen, Ida; Vethe, Nils Tore; Bergan, Stein & Hartmann, Anders [Show all 7 contributors for this article] (2009). Rimonabant Affects Cyclosporine A, but Not Tacrolimus Pharmacokinetics in Renal Transplant Recipients. Transplantation. ISSN 0041-1337. 87(8), p. 1221–1224.
• Bremer, Sara; Vethe, Nils Tore; Rootwelt, Helge & Bergan, Stein (2009). Expression of IMPDH1 is regulated in response to mycophenolate concentration. International Immunopharmacology. ISSN 1567-5769. 9(2), p. 173–180. doi: 10.1016/j.intimp.2008.10.017.
• Bremer, Sara; Vethe, Nils Tore; Rootwelt, H; Jorgensen, PF; Stenstrom, J & Holdaas, H [Show all 8 contributors for this article] (2009). Mycophenolate pharmacokinetics and pharmacodynamics in belatacept treated renal allograft recipients - a pilot study. Journal of Translational Medicine. ISSN 1479-5876. 7. doi: 10.1186/1479-5876-7-64.
• Vethe, Nils Tore; Bremer, Sara & Bergan, Stein (2008). IMP dehydrogenase basal activity in MOLT-4 human leukaemia cells is altered by mycophenolic acid and 6-thioguanosine. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 68, p. 277–285. doi: 10.1080/00365510701724871.
• Bremer, Sara; Mandla, Randeep; Vethe, Nils Tore; Rasmussen, Ingrid; Rootwelt, Helge & Line, PD [Show all 8 contributors for this article] (2008). Expression of IMPDH1 and IMPDH2 after transplantation and initiation of immunosuppression. Transplantation. ISSN 0041-1337. 85(1), p. 55–61. doi: 10.1097/01.tp.0000296854.68123.03.
• Falck, Pål; Vethe, Nils Tore; Åsberg, Anders; Midtvedt, Karsten; Bergan, Stein & Reubsaet, Jan Leo [Show all 7 contributors for this article] (2008). Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients. Nephrology, Dialysis and Transplantation. ISSN 0931-0509. 23, p. 1048–1053. doi: 10.1093/ndt/gfm632.
• Vethe, Nils Tore; Mandla, Randeep; Line, Pål Dag; Midtvedt, Karsten; Hartmann, A. & Bergan, Stein (2006). Inosine monophosphate dehydrogenase activity in renal allograft recipients during mycophenolate treatment. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 66.
• Vethe, Nils Tore & Bergan, Stein (2006). Determination of inosine monophosphate dehydrogenase activity in human CD4+cells isolated from whole blood during mycophenolic acid therapy. Therapeutic Drug Monitoring. ISSN 0163-4356. 28, p. 608–613.

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• Lauritzen, Trine; Munkhaugen, John; Lindahl, Sofia Helena; Bergan, Stein; Peersen, Kari & Husebye, Einar [Show all 7 contributors for this article] (2024). The effect of atorvastatin on mevalonate levels in blood plasma in patients with coronary heart disease and muscle side effects . European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 31(Supplement_1). doi: 10.1093/eurjpc/zwae175.357.
• Pivoriunas, Jonas; Engebretsen, Ingrid; Vethe, Nils Tore; Kristiansen, Oscar; Dammen, Toril & Fagerland, Morten Wang [Show all 9 contributors for this article] (2024). Statin adherence in coronary outpatients: a novel direct method compared with pharmacy registry data . European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 31(Supplement_1). doi: 10.1093/eurjpc/zwae175.063.
• Vethe, Nils Tore; Andersen, Anders Mikal; Gedde-Dahl, Tobias; Buechner, Jochen & Bergan, Stein (2024). Therapeutic Drug Monitoring of Intravenous Busulfan and Analytical Challenges due to the Drug Formulation Excipient PEG 400: Letter to the Editor. Therapeutic Drug Monitoring. ISSN 0163-4356. 46(3), p. 416–417. doi: 10.1097/FTD.0000000000001209.
• Pivoriunas, Jonas; Engebretsen, Ingrid; Vethe, Nils Tore; Kristiansen, Oscar; Dammen, Toril & Husebye, Einar [Show all 9 contributors for this article] (2024). Statin adherence in coronary outpatients: the relationship between a novel direct method and pharmacy registry data. Show summary

  Introduction An optimal method to assess adherence to statin therapy is needed. We developed a novel blood test to determine adherence to atorvastatin and simvastatin therapy. The relationship between statin adherence measured in blood and long-term adherence is yet to be defined. Purpose To compare statin adherence measured by single blood test with pharmacy registry data: i. the three months period prior to the blood test, and ii. from six months before until six months after the blood test. Methods In a cross-sectional study including 451 patients using either atorvastatin or simvastatin, a spot blood sample was collected median 18 months after a coronary heart disease event. Participants were unaware of the forthcoming statin analyses. Adherence (0 or 1 omitted dose) and reduced adherence, defined as ≥2 consecutively omitted doses of atorvastatin and simvastatin was determined by drug concentration measurements using liquid chromatography - tandem mass spectrometry. Study data was linked to the pharmacy registry. Indirect reduced adherence was defined as statin treatment gap exceeding 90 days. Results Thirty-nine (9%) out of 412 patients had reduced adherence to statins, determined by the novel blood test. Among patients classified as adherent by the blood test, only three (0.7%) had a treatment gap exceeding 90 days during the preceding three months. Correspondingly, of 39 patients with reduced adherence by the blood test, 11 (28%) had treatment gaps exceeding 90 days. The positive agreement between the methods was 96% and the negative agreement 42%. Among patients classified as adherent by the blood test, 21 (5%) had treatment gaps exceeding 90 days from six months before until six months after the blood test. Correspondingly, of 39 patients with reduced adherence by the blood test, 15 (39%) had at least one treatment gap exceeding 90 days. The positive agreement between measurements was 95% and the negative agreement 40%. Conclusions Among coronary patients classified as adherent by the statin blood test, registry data only identified three patients (0.7%) with a treatment gap exceeding 90 days in the three months prior to the blood test. The novel blood test emerges as a promising tool to identify patients adherent to statins, and thus may improve lipid management in clinical practice.

• Tuv, Silja Skogstad; Spigset, Olav; Jensen, Elena; Vethe, Nils Tore & Nordal, Kristin (2023). Nytt verktøy for tolkning av farmakogenetiske analyser. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 143(13). doi: 10.4045/tidsskr.23.0496. Full text in Research Archive
• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Andersen, Anders Mikal; Bergan, Stein & Husebye, Einar [Show all 7 contributors for this article] (2023). Atorvastatin lactonization is associated with statin-dependent muscular side effects in patient with coronary heart disease .
• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen & Andersen, Anders Mikal [Show all 10 contributors for this article] (2023). Atorvastatin lactone/acid ratios are promising biomarkers for statin dependent muscular side effects in patients with coronary heart disease. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30. doi: 10.1093/eurjpc/zwad125.340.
• Munkhaugen, John; Kristiansen, Oscar; Pivoriunas, Jonas; Fagerland, Morten; Bergan, Stein & Sverre, Elise Christine Bjørkholen [Show all 8 contributors for this article] (2023). Validation of a novel direct method to determine reduced adherence to atorvastatin therapy. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30. doi: 10.1093/eurjpc/zwad125.339.
• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Kristiansen, Oscar; Sverre, Elise Christine Bjørkholen & Andersen, Anders Mikal [Show all 10 contributors for this article] (2023). Atorvastatin lactone/acid ratios are promising biomarkers for statin dependent muscular side effects in patients with coronary heart disease.
• Lauritzen, Trine; Munkhaugen, John; Peersen, Kari; Sverre, Elise Christine Bjørkholen; Kristiansen, Oscar & Jensen, Elena Prunès [Show all 9 contributors for this article] (2022). Clinical and pharmacological characteristics in plasma and mononuclear blood cells in patients with coronary heart disease and low statin tolerance. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 29. doi: 10.1093/eurjpc/zwac056.177. Show summary

  Background Statin-associated muscle symptoms (SAMS) cover a broader range of clinical presentations, with normal or mildly elevated creatine kinase (CK) in blood, and is a prevalent challenge in clinical practice. Our understanding of the pathophysiology of SAMS remains largely unknown. Purpose To gain new knowledge on the molecular effects of atorvastatin in plasma and blood cells in patients with coronary heart disease (CHD) and SAMS, and to identify potential diagnostic biomarkers for statin-dependent SAMS. Methods In 2019, 71 consecutively recruited CHD patients with self-perceived SAMS were randomised to 7-weeks double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was individual mean difference in muscle symptom intensity between treatment periods, measured weekly with a Visual Analogue Scale (VAS) (0= no to 10=maximal symptoms). Twenty patients were categorised as having statin-dependent SAMS and the remaining as non-SAMS. During trial and post-trial follow-up period, a subgroup of statin-dependent SAMS, who did not tolerate statins (N=7) or only rosuvastatin 5mg/day (N=2) was identified. Atorvastatin metabolites in plasma and peripheral blood mononuclear cells (PBMC) were measured with liquid chromatography tandem mass spectrometry in blood drawn two hours after tablet intake at the last day of the atorvastatin treatment period. Statistical analyses were performed with SPSS. Results Clinical and pharmacological characteristics in patients with low statin-tolerance (N=9) and those without (N=62) are summarised in Figure 1. The reduction in LDL cholesterol (LDL-C) from the placebo period to the atorvastatin period was significantly lower in the group with low statin tolerance, despite confirmed adherence to allocated treatment. The ratio between the sum of all atorvastatin- lactones and acids (SumLactones/SumAcids) was significantly higher in the group with low statin tolerance both in plasma and PBMC analyses compared to those who tolerated statins. The atorvastatin lactone and acid ratio (AL/AA) was borderline significant in both plasma and PBMC. ROC-analyses of these four variables are displayed in Figure 2. Areas under the curves (AUCs) are 0.71 for the sumLactones/sumAcids both in plasma and PBMC, and 0.69 for the AL/AS in plasma and PBMC. There were no significant differences between the groups regarding age, gender or known pharmacogenetic variants (CYP3A and SLCO1B1) or in the differences in creatine kinase (CK) level between the atorvastatin and placebo treatment periods. Conclusions The ratio between atorvastatin lactones and acids in plasma and in mononuclear blood cells is associated with low statin tolerance in patients with CHD. Excess lactone relative to acid metabolites may be involved in the pathophysiology of SAMS. Future studies in muscle tissue may further elucidate the relationship between SAMS and atorvastatin metabolites and other biomarkers in these patients.

• Robertsen, Ida; Åsberg, Anders; Jenssen, Trond Geir; Gence, Berfin; Vethe, Nils Tore & Midtvedt, Karsten [Show all 8 contributors for this article] (2021). Increased systemic exposure of once-daily tacrolimus in renal transplant recipients on marine omega-3 fatty acid supplementation. Transplant International. ISSN 0934-0874. doi: 10.1111/tri.13917.
• Brede, Cato; Vethe, Nils T. & Skadberg, Øyvind (2021). The Question of Accuracy Versus Interlaboratory Agreement for Monitoring the Immunosuppressants Everolimus and Sirolimus. Therapeutic Drug Monitoring. ISSN 0163-4356. 43(3), p. 444–446. doi: 10.1097/FTD.0000000000000892.
• Tuv, Silja Skogstad; Nordal, Kristin; Vethe, Nils Tore & Bergan, Stein (2019). Farmakogenetikk i persontilpasset legemiddelbehandling. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 139(8), p. 1–5. doi: 10.4045/tidsskr.19.0055.
• Robertsen, Ida; Åsberg, Anders; Granseth, Tone; Vethe, Nils Tore; Akhlaghi, Fatemeh & Ghareeb, Mwlod [Show all 10 contributors for this article] (2013). ROSUVASTATIN IS A POTENT LIPID-LOWERING STATIN IN RENAL TRANSPLANT RECIPIENTS RECEIVING EVEROLIMUS. Transplant International. ISSN 0934-0874. 26, p. 50–50.
• Bremer, Sara; Johansson, E.D.; Pham, L.; Vethe, Nils Tore; Line, Pål Dag & Midtvedt, Karsten [Show all 10 contributors for this article] (2013). NFAT-Regulated Cytokine Expression During Tacrolimus Therapy Early After Transplantation. Therapeutic Drug Monitoring. ISSN 0163-4356. 35(5), p. 668–668.
• Sæves, Ingjerd; Vethe, Nils Tore; Line, Pål Dag; Fosby, Bjarte & Bergan, Stein (2011). Variable pharmacokinetics of prednisolone and prednisone in liver transplant recipients early after transplantation. Therapeutic Drug Monitoring. ISSN 0163-4356. 33(4), p. 555–555.
• Vethe, Nils Tore; Ali, Mohamad A. & Bergan, Stein (2011). Simultaneous determination of IMPDH activity and purine bases in lymphocytes by LC-MS/MS: Assessment of mycophenolate pharmacodynamics. Therapeutic Drug Monitoring. ISSN 0163-4356. 33(4), p. 541–541.
• Vethe, Nils Tore; Quiogue, A.M.; Hotvedt, S.A.; Gjerdalen, Laila Carol & Bergan, Stein (2011). Precise measurement of thiopurines by LC-MS/MS: usage of isotope-labelled internal standards and normalization to packed erythrocyte volume. Therapeutic Drug Monitoring. ISSN 0163-4356. 33(4), p. 553–553.
• Amundsen, Rune; Åsberg, Anders; Robertsen, Ida; Vethe, Nils Tore; Bergan, Stein & Hartmann, Anders [Show all 7 contributors for this article] (2009). Rimonabant Affects Cyclosporine A, but Not Tacrolimus Pharmacokinetics in Renal Transplant Recipients. American Journal of Transplantation. ISSN 1600-6135. 9, p. 394–395.
• Bremer, Sara; Vethe, Nils Tore; Rootwelt, Helge; Jørgensen, Pål Foyn; Stenstrøm, Jean & Holdaas, Hallvard [Show all 8 contributors for this article] (2009). Mycophenolate Pharmacodynamics is Altered with Time Since Transplantation. Therapeutic Drug Monitoring. ISSN 0163-4356. 31(5), p. 620–620.
• Amundsen, Rune; Åsberg, Anders; Robertsen, Ida; Vethe, Nils Tore; Bergan, Stein & Midtvedt, Karsten (2009). Rimonabant Affects Cyclosporine A, but Not Tacrolimus Pharmacokinetics in Renal Transplant Recipients.
• Falck, Pål; Vethe, Nils Tore; Åsberg, Anders; Midtvedt, Karsten; Bergan, Stein & Reubsaet, Jan Leo [Show all 7 contributors for this article] (2007). Cinacalcet influences the pharmacokinetics of tacrolimus but not cyclosporine or mycophenolate in stable renal transplant recipients.
• Holdaas, Hallvard; Falck, Pål; Vethe, Nils Tore; Åsberg, Anders; Reubsaet, Jan Leo & Bergan, Stein [Show all 7 contributors for this article] (2007). Impact of cinacalcet on pharmacokinetics of calcineurin inhibitors in renal transplanted patients.

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