THE INFLUENCE OF PREGNANCY ON THE BIOTRANSFORMATION AND URINARY-EXCRETION OF METHOXYPHENAMINE IN MICE

(i) The urinary elimination of methoxyphenamine (MPA) and its metaboli tes in underivatized samples was examined after single and multiple or al administration to pregnant and non-pregnant mice by GLC and GLC-MS. (ii) The major metabolite O-desmethylmethoxyphenamine (ODMP), along w ith lesser amounts of N-desmethylmethoxyphenamine (NDMP) and 2-hydroxy amphetamine (2OH), were the only metabolites detected in urine extract s of pregnant and nonpregnant mice. 5-Hydroxymethoxyphenamine (5HMP) w as not detected. Enzyme hydrolysis did not increase the recovery of ei ther substrate or metabolites in either the pregnant or non-pregnant a nimals. The results show that MPA metabolism in the Swiss-Webster mous e is distinctly different from that seen in man and other laboratory a nimals. (iii) The mean MPA:ODMP ratio in day-6 urine from pregnant mic e after a single dose was 0.31 +/- 0.04. The NDMP:ODMP ratios were les s than 0.10 in all samples. Nonpregnant mice urine had equivalent amou nts of MPA, NDMP, ODMP, and 2OH after multiple dosing. (iv) While mult iple dosing and pregnancy did not alter either the urinary recovery or profile of the metabolites detected, there was a linear decrease in t he MPA:ODMP ratio during gestation. (v) MPA was extensively metabolize d to ODMP in the male mice, and the MPA:ODMP ratio of 0.41 was slightl y higher than that observed in the pregnant and non-pregnant females.