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- W2116760577 abstract "Abstract1. The disposition of AY-30,068 (I), a new tetrahydrocarbazole analgesic drug, was studied in mice, rats, dogs, rhesus monkeys, and man.2. Oral doses of the 14C-labelled drug in aqueous solution were well absorbed in rodents, but absorption of oral doses of the crystalline drug in dogs was poor. Due to the virtual absence of serum metabolites in rats and dogs, the bioavailability of I was nearly identical to the extent of absorption. Although a small first-pass effect was observed in mice, unchanged I represented a major portion of serum radioactivity.3. A linear increase in the serum concentrations of I occurred at doses between 0.05 and 25 mg/kg in rats, 0.1 and 50 mg/kg in dogs, and 1–160 mg in man. In rhesus monkeys given a 0.5 mg/kg oral dose, the Cmax and AUC of I were similar to values obtained following a corresponding dose in dogs.4. After i.v. administration of a 1.0 mg/kg dose the terminal elimination half-life (t1/2β) of I was 4 h in mice and 9–10h in rats and dogs. In rodents, dogs, and several human subjects, the elimination of I was interrupted by secondary peaks. Enterohepatic circulation was confirmed in bile duct cannulated rats, where the t1/2β of I was decreased to 2.4 h. In rodents the serum clearance and apparent volume of distribution of I were 0.04–0.21/kg. h and 0.5–0.81/kg, respectively, and 0.61/kg.h and 9.81/kg in dogs.5. In rodents and dogs dosed with 14C-labelled I, radioactivity was excreted almost entirely in the faeces. No unchanged I was detected in rat bile, while about 70% of the radioactivity corresponded to conjugates of parent drug." @default.
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- W2116760577 date "1989-01-01" @default.
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- W2116760577 title "Disposition of a new tetrahydrocarbazole analgesic drug in laboratory animals and man" @default.
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- W2116760577 doi "https://doi.org/10.3109/00498258909043156" @default.
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