Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects.
OBJECTIVE
Rifampin (INN, rifampicin) causes several drug interactions with coadministered antidiabetic drugs. Rosiglitazone is a novel thiazolidinedione antidiabetic 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.


METHODS
In an open-label, randomized, 2-way crossover study, 10 healthy Korean male subjects were treated once daily for 6 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 ng. h/mL versus 991.5 ng. h/mL, P <.001) and the mean elimination half-life from 3.9 to 1.5 hours (P <.001). The peak plasma concentration of rosiglitazone was significantly decreased by rifampin (537.7 ng/mL versus 362.3 ng/mL, P <.01). The apparent oral clearance of rosiglitazone increased about 3-fold after rifampin treatment (2.8 L/h versus 8.5 L/h, P <.001).


CONCLUSIONS
This study showed that rifampin affected the disposition of rosiglitazone in humans, probably by the induction of cytochrome P450 (CYP) 2C8 and, to a lesser extent, CYP2C9. Therefore caution should be exercised during the coadministration of rifampin and rosiglitazone.
Departmernts of Pharmacology and Endocrinology, Gil Medical Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, South Korea. jypark@gachon.ac.kr
Ji-Young
JY
Park
Kyoung-Ah
KA
Kim
Mun-Ho
MH
Kang
Su-Lyun
SL
Kim
Jae-Gook
JG
Shin
D000328:Adult; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D018592:Cross-Over Studies; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D012293:Rifampin / Q000097:blood* / Q000493:pharmacokinetics*; D000077154:Rosiglitazone; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000097:blood* / Q000493:pharmacokinetics*
D045162:Thiazolidinediones; D000077154:Rosiglitazone; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D012293:Rifampin