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KMID : 0043320010240040333
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Archives of Pharmacal Research
2001 Volume.24 No. 4 p.333 ~ p.337
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Pharmacokinetics of Diltiazem and its Ma;or Metabolite, Deacetyldiltiazem after Oral Admirlistration of Diltiazem in Mild and Medium Folate-Induced Renal Failure Rabbits
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Choi JS
Lee JH/Burm JP
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Abstract
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The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite, deacetyldilt- iazem (DAD) were studied after oral administration of DTZ to normal rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10 mg/kg was given to the rabbits either orallγ (n=6). Plasma concentrations of DTZ and DAD were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curries (AUC) and maximum plasma concentration (Cmax) of DTZ were significantly increased in mild and medium folate-induced renal failure rabbits. The metabolite ratio of the DTZ to DAD were significantly decreased in mild and medium folate-induced renal failure rabbits. The volume of distribution (Vd) and total body clearance (CL)t of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits. The elimi-nation rate constant (β) of DTZ was significantly decreased in folate-induced renal failure rabbits, but that of DAD was significantly increased. These findings suggest that the hepatic metabolism of DTZ was inhibited and the Vd, CLt, and βof DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits.
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