Abstract
The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite, deacetyldiltiazem (DAD) were studied after oral administration of DTZ to normal rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10mg/kg was given to the rabbits either orally (n = 6). Plasma concentrations of DTZ and DAD were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (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 (CLt) of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits. The elimination 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 β of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits.
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Choi, J.S., Lee, J.H. & Burm, J.P. Pharmacokinetics of Diltiazem and its major metabolite, Deacetyldiltiazem after oral administration of Diltiazem in mild and medium folate-induced renal failure rabbits. Arch Pharm Res 24, 333–337 (2001). https://doi.org/10.1007/BF02975102
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DOI: https://doi.org/10.1007/BF02975102