The influence of pregnancy on the biotransformation and urinary excretion of methoxyphenamine in mice

✍ Scribed by Brian C. Foster; D. Lynden Wilson; Terry D. Cyr; James Moffatt; Harpal S. Buttar

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 610 KB
• Volume: 16
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510160102

✦ Synopsis

i) The urinary elimination of methoxyphenamine (MPA) and its metabolites in underivatized samples was examined after single and multiple oral administration to pregnant and non-pregnant mice by GLC and GLC-MS. (ii) The major metabolite 0-desmethylmethoxyphenamine (ODMP), along with lesser amounts of N-desmethylmethoxyphenamine (NDMP) and 2-hydroxyamphetamine (ZOH), were the only metabolites detected in urine extracts of pregnant and nonpregnant mice. 5-Hydroxymethoxyphenamine (5HMP) was not detected. Enzyme hydrolysis did not increase the recovery of either substrate or metabolites in either the pregnant or non-pregnant animals. The results show that MPA metabolism in the Swiss-Webster mouse is distinctly different from that seen in man and other laboratory animals. (iii) The mean MPA : ODMP ratio in day-6 urine from pregnant mice after a single dose was 0.31 kO.04. The NDMP: ODMP ratios were less than 0.10 in all samples. Nonpregnant mice urine had equivalent amounts of MPA, NDMP, ODMP, and 2 0 H after multiple dosing. (iv) While multiple dosing and pregnancy did not alter either the urinary recovery or profile of the metabolites detected, there was a linear decrease in the MPA: ODMP ratio during gestation. (v) MPA was extensively metabolized to ODMP in the male mice, and the MPA: ODMP ratio of 0.41 was slightly higher than that observed in the pregnant and non-pregnant females.

KEY WORDS Methoxyphenamine Pregnancy Mouse Biotransformation Metabolism

Introduction

The focus of this study was to determine whether pregnancy alters the route and extent of biotransformation of the phenotypic marker methoxyphenamine *Presented in part at the International Society for the Study of Xenobiotics Fifth European Meeting,