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Effect of rifampin on the pharmacokinetics of rosiglitazone in korean healthy subjects
Author(s) -
Park J.,
Kim K.,
Jung W.,
Kim S.,
Shin J.
Publication year - 2004
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 - 10.1016/j.clpt.2003.11.129
Subject(s) - rosiglitazone , medicine , pharmacokinetics , rifampicin , pharmacology , placebo , repaglinide , drug , crossover study , endocrinology , type 2 diabetes , diabetes mellitus , tuberculosis , receptor , alternative medicine , pathology
Background and Objective Rifampin (INN, rifampicin) caused several drug interactions with several co‐administered antidiabetic drugs. Rosiglitazone is a novel thiazolinedione anti‐diabetic drug but little is known about the drug interaction between rifampin and rosiglitazone. Our objective was to investigate the effect of rifampin on the pharmacokinetics of rosiglitazone in humans. Method In a randomized two‐way crossover study, 10 healthy Korean male subjects were treated once daily for six days with 600 mg rifampin or with placebo. On day 7, a single dose of 8 mg rosiglitazone was administered orally. Plasma rosiglitazone concentrations were measured. Results Rifampin significantly decreased the mean area under the plasma concentration–time curve for rosiglitazone by 65% (2947.9 versus 991.5 ng hr/ml; P <0.001) and the mean elimination half‐life from 3.9 to 1.5 hours (P<0.001). The peak plasma concentration of rosiglitazone was significantly decreased by rifampin (537.7 versus 362.3 ng/ml; P<0.02). The apparent oral clearance of rosiglitazone increased about three‐fold after rifampin treatment (2.8 versus 8.5 L/h; P<0.001). Conclusion This study showed that rifampin affects the disposition of rosiglitazone in humans, probably by the induction of CYP2C8 and to a lesser extent CYP2C9. Therefore, caution should be exercised during the co‐administration of rifampin and rosiglitazone. Clinical Pharmacology & Therapeutics (2004) 75 , P34–P34; doi: 10.1016/j.clpt.2003.11.129