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Sex‐differences in the disposition of substituted benzamides: Pharmacokinetics of a gastroprokinetic agent (4‐amino‐5‐chloro‐2‐[2‐(methylsulfinyl) ethoxy]‐N‐[2‐(diethylamino)ethyl] benzamide hydrochloride) (ML‐1035) in male and female New Zealand white rabbits
Author(s) -
Rao Niranjan,
Otis Kenneth W,
Hwang KinKai
Publication year - 1992
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510130906
Subject(s) - benzamide , pharmacokinetics , volume of distribution , bioavailability , oral administration , chemistry , hydrochloride , dosing , pharmacology , alkoxy group , disposition , medicine , endocrinology , stereochemistry , biochemistry , psychology , social psychology , alkyl , organic chemistry
The disposition of 4‐amino‐5‐chloro‐2‐[2‐(methylsulfinyl)ethoxy]‐ N ‐[2‐(diethylamino) ethyl] benzamide hydrochloride (ML‐1035) following intravenous (10 mg kg −1 ) and oral (200 mg kg −1 ) dosing was investigated in male and female New Zealand white rabbits. After intravenous dosing ML‐1035 was eliminated with a half‐life of 1·45 ± 0·49 h in males and 0·79 ± 0·08 h in females. Volume of distribution at steady‐state was 2·08 ± 0·98 1 kg −1 in males and 9·11 ± 5·86 1 kg −1 in females. Clearance averaged 2·99 ± 1·11 1 h −1 kg −1 in males and 16·73 ± 7·29 1 h −1 kg −1 in females. All pharmacokinetic parameters were significantly different between males and females ( p <0·05). Absolute bioavailability after oral administration was 7·35 per cent for males and 12·31 per cent for females, suggesting that ML‐1035 undergoes significant first‐pass elimination. Plasma area under the curve for the metabolites of ML‐1035 after both oral and intravenous administration were also different between the two sexes. These data suggest that the disposition of ML‐1035 shows significant differences between male and female rabbits.