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KMID : 0369819920220040301
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Jorunal of Korean Pharmaceutical Sciences
1992 Volume.22 No. 4 p.301 ~ p.306
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Effect of Phenobarbital on the Metabolite Kinetics of Diltiazem in Rats
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이용복/Lee YB
고익배/심창구/김신근/이민화/Koh IB/Shim CK/Kim SK/Lee MH
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Abstract
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The influence of phenobarbital (PB) pretreatment (75 mg/kg/day, i.p. for 4 days) on the metabolite kinetics of diltiazem (DTZ) was studied in rats in order to elucidate the effect of esterase induced by PB on the formation of DTZ to desacetyldiltiazem (DAD), DAD was injected via portal vein (3 mg/kg) to the control and PB-pretreated rats, The intrinsic hepatic clearance of DAD was significantly increased by PB pretreatment and the absolute bioavailability of DAD was significantly decreased in the PB-pretreated rats. According to the hepatic biotransformation model of DTZ, the fraction of systemic clearance of DTZ which forms DAD (Gmi) was different from that of DTZ which furnishes the available DAD to the systemic circulation (Fmi) in control rats. This result shows that DTZ was suspected of the sequential hepatic first-pass metabolism. On the other hand, PB pretreatment enhanced the Gmi value of DTZ by 44%. It may be concluded that the deacetylation of DTZ to DAD in rats is increased by the esterase induced by PB but the transfer rate of DAD immediately formed from DTZ into systemic circulation is not affected by PB due to the 27% decreased absolute bioavailability of DAD resulting from PB pretreatment.
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KEYWORD
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