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
✍ Scribed by Niranjan Rao; Kenneth W Otis; Kin-Kai Hwang
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 577 KB
- Volume
- 13
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
The disposition of 4-amino-5-chloro-2-[ 2-(methylsulfinyl)ethoxy ] -N-[ 2-(diethylamino) ethyl] benzamide hydrochloride (ML-1035) following intravenous (10 mg kg-I) and oral (200 mg kg-I) dosing was investigated in male and female New Zealand white rabbits. After intravenous dosing ML-1035 was eliminated with a half-life of 1.45kO.49 h in males and 0.79kO-08 h in females. Volume of distribution at steady-state was 2.08&0.98 1 kg-I in males and 9.11 k5.861 kg-' in females. Clearance averaged 2*99+1-111h-1kg-1 inmalesand 16-73k7.291h-'kg-'in females. Allpharmacokinetic 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.