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 AUC0-12 (area under curve, 0-12h) by 9.5 +/- 18% (p = 0.013) and Cmax (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.
Asberg
A
A
Medical Department, The National Hospital, Oslo, Norway. anderas@klinmed.uio.no
Hartmann
A
A
Fjeldså
E
E
Bergan
S
S
Holdaas
H
H
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D019540:Area Under Curve; D000069059:Atorvastatin; D000077552:Basiliximab; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006538:Heptanoic Acids / Q000493:pharmacokinetics*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000493:pharmacokinetics; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D011758:Pyrroles / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins
D000911:Antibodies, Monoclonal; D006538:Heptanoic Acids; D007166:Immunosuppressive Agents; D011758:Pyrroles; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D011239:Prednisolone; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases