期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 42, 期 2, 页码 222-228出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/00912700222011148
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The authors assessed the mutual influence of the immunosuppressant everolimus (Certican) and the HMG-CoA reductase inhibitors atorvastatin and pravastatin when coadministered based on pharmacokinetic and pharmacodynamic measures. In this randomized, open-label, three-way crossover study, 24 healthy men received three single-dose oral treatments: 2 mg everolimus, 20 mg atorvastatin (n = 12) or 20 mg pravastatin (n = 12), and the respective statin coadministered with everolimus. Consecutive treatments were separated by a 14-day washout. The pharmacokinetics of all three drugs and total HMG-CoA reductase inhibitors were measured. Everolimus Cm was reduced by 9% and 10% with atorvastatin and pravastatin coadministration; the corresponding decreases in everolimus AUC were 5% and 6%, respectively: Everolimus coadministration increased the C-max of atorvastatin by 11 % but had no influence on atorvastatin AUC. Coadministration of everolimus with pravastatin was associated with a 10% decrease in pravastatin C. and a 5% decrease in the AUC. The elimination half-lives of the two statins were unaffected by everolimus. Changes in total HMG-CoA reductase inhibitors in plasma exhibited generally similar patterns as for the parent statin exposures. Single-dose administrations of everolimus with either atorvastatin or pravastatin did not influence the pharmacokinetics of everolimus, atorvastatin, pravastatin, or total HMG-CoA reductase inhibitors in plasma to a clinically relevant extent. 2002 the American College of Clinical Pharmacology.
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