Bilateral Pharmacokinetic Interaction Between Cyclosporine A and Atorvastatin in Renal Transplant Recipients

Authors: Åsberg A.¹; Hartmann A.¹; Fjeldså E.¹; Bergan S.²; Holdaas H.¹

Source: American Journal of Transplantation, Volume 1, Number 4, November 2001 , pp. 382-386(5)

Publisher: Wiley-Blackwell

Abstract:

Atorvastatin is increasingly used as a cholesterol-lowering agent in solid organ transplant recipients receiving cyclosporine A (CsA). However, the potential bilateral pharmacokinetic interaction between atorvastatin and CsA in renal transplant recipients has not previously been examined.

Baseline 12-h CsA pharmacokinetic investigation was performed in 21 renal transplant recipients and repeated after 4 weeks of atorvastatin treatment (10 mg/d). At week 4, 24-h pharmacokinetics of atorvastatin was also performed. All patients received basiliximab induction followed by CsA and prednisolone immunosuppression.

Compared with historic controls, CsA-treated patients showed, on average, sixfold higher plasma HMG-CoA reductase inhibitory activity after 4 weeks of atorvastatin treatment (p < 0.05). Atorvastatin had a moderate effect on the pharmacokinetics of CsA and reduced the AUC_0-12 (area under curve, 0–12 h) by 9.5 ± 18% (p = 0.013) and C_max (maximal concentration) by 13.5 ± 24% (p = 0.009), while C₁₂ (trough level) was unchanged (p = 0.42). Total and LDL cholesterol decreased by 26.8 ± 8.4% (p < 0.0001) and 41.5 ± 11.0% (p < 0.0001), respectively.

Bilateral pharmacokinetic interaction between atorvastatin and CsA resulted in sixfold higher plasma HMG-CoA reductase inhibitory activity, but only a moderate decrease in systemic exposure of CsA.

Keywords: Atorvastatin; cyclosporine A; interaction; lipids; pharmacokinetics; renal transplantation

Language: English

Document Type: Original article

DOI: http://dx.doi.org/10.1034/j.1600-6143.2001.10415.x

Affiliations: 1: Laboratory for Renal Physiology, Section of Nephrology, Medical Department, and 2: Institute of Clinical Biochemistry, The National Hospital, N-0027 Oslo, Norway *

Publication date: 2001-11-01

• In this: publication
• By this: publisher
• In this Subject: Microbiology ,  Allergy & Immunology ,  Medicine (General) ,  Surgery
• By this author: Åsberg A. ;  Hartmann A. ;  Fjeldså E. ;  Bergan S. ;  Holdaas H.

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