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Effects of Single Dose Rifampin on the Pharmacokinetics of Fluvastatin in Healthy Volunteers
Author(s) -
Xiang Yue,
Okochi Hideaki,
Kozachenko Ivan,
Sodhi Jasleen K.,
Frassetto Lynda A.,
Benet Leslie Z.
Publication year - 2021
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2268
Subject(s) - fluvastatin , pharmacokinetics , medicine , pharmacology , simvastatin
The objective of this study was to determine the effects of the OATP inhibitor rifampin on pharmacokinetic of Biopharmaceutics Drug Disposition Classification System Class 1 compound fluvastatin. A crossover study was carried out in 10 healthy subjects who were randomized to 2 phases to receive fluvastatin 20 mg orally alone and following a 30‐minute 600 mg i.v. infusion of rifampin. The results demonstrated that i.v. rifampin increased the mean area under the plasma fluvastatin concentration–time curve (AUC 0–∞ ) by 255%, mean peak plasma concentration (C max ) by 254%, decreased oral volume of distribution by 71%, whereas the mean elimination terminal half‐life (T 1/2 ), mean absorption time (MAT), and time to peak concentration (T peak ) of fluvastatin did not significantly change. The study demonstrated that rifampin exhibited a significant drug interaction with fluvastatin. The mechanism of the increased plasma concentrations is likely due to inhibition of OATP transporters in hepatocytes.