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Pharmacokinetic and Pharmacodynamic Assessments of HMG‐CoA Reductase Inhibitors When Coadministered with Everolimus
Author(s) -
Kovarik John M.,
Hartmann Stefan,
Hubert Martine,
Berthier Stephane,
Schneider Werner,
Rosenkranz Bernd,
Rordorf Christiane
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700222011148
Subject(s) - atorvastatin , pravastatin , everolimus , pharmacology , rosuvastatin , pharmacokinetics , pharmacodynamics , hmg coa reductase , medicine , hydroxymethylglutaryl coa reductase , crossover study , statin , reductase , chemistry , cholesterol , placebo , biochemistry , alternative medicine , pathology , enzyme
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 C max 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 max 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.