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
| Autor: | Niranjan Rao, Kin-Kai Hwang, Kenneth W. Otis |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Hydrochloride medicine.drug_class Metabolic Clearance Rate Metoclopramide Pharmaceutical Science Administration Oral Biological Availability Pharmacology chemistry.chemical_compound Structure-Activity Relationship Sex Factors Pharmacokinetics Oral administration Internal medicine Medicine Antiemetic Animals Pharmacology (medical) Benzamide Chromatography High Pressure Liquid Volume of distribution Gastric emptying business.industry Area under the curve General Medicine Endocrinology chemistry Injections Intravenous Female Rabbits business |
| Zdroj: | Biopharmaceuticsdrug disposition. 13(9) |
| ISSN: | 0142-2782 |
| Popis: | 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 l kg-1 in males and 9.11 +/- 5.86 l kg-1 in females. Clearance averaged 2.99 +/- 1.11 l h-1 kg-1 in males and 16.73 +/- 7.29 l 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. |
| Databáze: | OpenAIRE |
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