Pharmacokinetics of carvedilol (DQ-2466) in healthy subjects.

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Carvedilol is a newly developed β-blocking agent with vasodilating activities. The pharmacokinetics of carvedilol has been studied in healthy subjects following the single and multiple oral administration of the drug. In the single oral study, it was clear that the disposition of carvedilol is adequately described by a two-compartment model with first order absorption. Carvedilol was rapidly absorbed within 1.6 hr following oral dosing. The half-lives ranging from 6 to 14 hr are estimated. The study indicated that carvedilol follows linear pharmacokinetics with a slight deviation from linearity in the range of 5 to 60 mg dose. The deviation is attributed to about 4-fold inter-individual variation observed for AUC. Carvedilol is not excreted into urine, suggesting that the drug is eliminated from plasma primarily by metabolism. It is considered that the wide interindividual variation is attributed to variaton in hepatic first-pass metabolism of carvedilol. The plasma level of carvedilol glucuronide was about 2-fold greater than that of carvedilol and desmethyl carvedilol was 5 times lower than that of carvedilol. During the multiple oral administration of carvedilol for 14 days at a daily dose of 20 mg, plasma profiles showed no accumulation of the drug. The predicted steady-state for carvedilol is attained on day 11, and Css (max) and Css (min) values for the drug are calculated to be 46.4 and 2.1 ng/ml, respectlvely.