Abstract
Background and 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. Method: 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). Conclusion: 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.
| Original language | English |
|---|---|
| Pages (from-to) | 157-162 |
| Number of pages | 6 |
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 75 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2004 Mar 1 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects. / Park, Ji-Young; Kim, Kyoung Ah; Kang, Mun Ho; Kim, Su Lyun; Shin, Jae Gook.
In: Clinical Pharmacology and Therapeutics, Vol. 75, No. 3, 01.03.2004, p. 157-162.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of rifampin on the pharmacokinetics of rosiglitazone in healthy subjects
AU - Park, Ji-Young
AU - Kim, Kyoung Ah
AU - Kang, Mun Ho
AU - Kim, Su Lyun
AU - Shin, Jae Gook
PY - 2004/3/1
Y1 - 2004/3/1
N2 - Background and 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. Method: 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). Conclusion: 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.
AB - Background and 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. Method: 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). Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=1542286164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1542286164&partnerID=8YFLogxK
U2 - 10.1016/j.clpt.2003.10.003
DO - 10.1016/j.clpt.2003.10.003
M3 - Article
C2 - 15001966
AN - SCOPUS:1542286164
VL - 75
SP - 157
EP - 162
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 3
ER -