Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients

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 C-12 (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.