Bilateral Pharmacokinetic Interaction Between Cyclosporine A and Atorvastatin in Renal Transplant Recipients
| Autor: | Ellen Fjeldså, Anders Hartmann, Stein Bergan, Anders Åsberg, Hallvard Holdaas |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male Basiliximab Prednisolone Recombinant Fusion Proteins Atorvastatin Cmax Pharmacology Pharmacokinetics medicine Humans Immunology and Allergy Drug Interactions Pyrroles Pharmacology (medical) Kidney transplantation Aged Transplantation business.industry Antibodies Monoclonal Middle Aged medicine.disease Kidney Transplantation Hydroxymethylglutaryl-CoA reductase Heptanoic Acids Area Under Curve Cyclosporine Trough level Female Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) business Immunosuppressive Agents medicine.drug |
| Zdroj: | American Journal of Transplantation. 1:382-386 |
| ISSN: | 1600-6135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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