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This study investigated the effect of long-term administration of pioglitazone on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats coadministered pioglitazone (0.5 mg/kg) or pretreated with pioglitazone (0.5 mg/kg) for 3 and 9 days. Compared to oral control group, the presence of pioglitazone significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) of verapamil by 48.6% (coad), 61.1% (3 days) and 56.5% (9 days), and the peak concentration (Cmax) by 65.1% (coad), 76.8% (3 days) and 66.4% (9 days). The absolute bioavailability (AB%) of verapamil was significantly (p<0.05) higher by 6.2% (coad), 6.7% (3 days), 6.5% (9 days) compared to control (4.2%), and presence of pioglitazone
was no significant change in the terminal half-life (t1/2) and the time to reach the peak concentration (Tmax) of verapamil. Our results indicate that pioglitazone significantly enhanced oral bioavailability of verapamil in rats, implying that presence of pioglitazone could be effective to inhibit the CYP3A4-mediated metabolism of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with pioglitazone.
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참고문헌 (25)
참고문헌 신청
Chilcott J / 20
Dominic JA / 1981 / The pharmacology of verapamil. III. Pharmacokinetics in normal subjects after intravenous drug administration / J Cardiovasc Pharmacol 3 : 25 ~ 38
Eichelbaum M / 1979 / The metabolism of D,L(14C) verapamil in man / Drug Metab Dispos 7 : 145 ~ 148
Eichelbaum M / 1980 / Effects of verapamil on PR intervals in relation to verapamil plasma levels following single i.v. and oral administration and during chronic treatment
Eichelbaum M / 1980 / Influence of mesocaval shunt surgery on verapamil kinetics, bioavailability and response / Br J Clin Pharmacol 10 : 527 ~ 529
Dominic JA / 1981 / The pharmacology of verapamil. III. Pharmacokinetics in normal subjects after intravenous drug administration / J Cardiovasc Pharmacol 3 : 25 ~ 38
Eichelbaum M / 1979 / The metabolism of D,L(14C) verapamil in man / Drug Metab Dispos 7 : 145 ~ 148
Eichelbaum M / 1980 / Effects of verapamil on PR intervals in relation to verapamil plasma levels following single i.v. and oral administration and during chronic treatment
Eichelbaum M / 1980 / Influence of mesocaval shunt surgery on verapamil kinetics, bioavailability and response / Br J Clin Pharmacol 10 : 527 ~ 529
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