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  • Title: Comparative pharmacokinetics of a new benzamide neuroleptic drug in rats, dogs and monkeys using a stable isotope technique.
    Author: Higuchi S, Yokoi K, Soeishi Y, Kawamura S.
    Journal: Xenobiotica; 1986 Jan; 16(1):79-86. PubMed ID: 2868578.
    Abstract:
    Comparative pharmacokinetics of a new benzamide neuroleptic drug, cis-N-(1-benzyl-2-methylpyrrolidine-3-yl)-5-chloro-2-methoxy-4-met hylamino benzamide (NBND) was studied in rats, dogs and monkeys using two deuterium-labelled compounds. NBND and 2H3-NBND, which showed no biological isotope effect, were co-administered p.o. and i.v. to rats, dogs and monkeys, and the plasma concentrations of unchanged drugs were simultaneously determined by g.l.c.-chemical ionization mass spectrometry with 2H7-NBND as an internal standard. The plasma half-lives (t1/2 beta) after i.v. administration were 1.6, 4.7 and 2.2 h in rats, dogs and monkeys at a dose of 0.2 mg/kg. Plasma clearances were 4.3, 1.7 and 1.4 l/h per kg in rats, dogs and monkeys. Absorption rate constants (Kab) were 1.1, 0.58 and 0.54 per h in rats, dogs and monkeys, at doses of 10, 3 and 5 mg/kg, respectively. Absolute bioavailabilities were 0.8, 9.5 and 1.3% in rats, dogs and monkeys, suggesting that all these species showed large first-pass effects, probably due to hepatic metabolism.
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