The influence of pregnancy on the biotransformation and urinary excretion of methoxyphenamine in mice.
(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 O-desmethylmethoxyphenamine (ODMP), along with lesser amounts of N-desmethylmethoxyphenamine (NDMP) and 2-hydroxyamphetamine (2OH), were the only metabolites detected in urine extracts of pregnant and non-pregnant 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 +/- 0.04. The NDMP:ODMP ratios were less than 0.10 in all samples. Non-pregnant mice urine had equivalent amounts of MPA, NDMP, ODMP, and 2OH 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.
Foster
B C
BC
Sir Frederick Banting Research Centre, Health Protection Branch, Health Canada, Ottawa, Ontario.
Wilson
D L
DL
Cyr
T D
TD
Moffatt
J
J
Buttar
H S
HS
D000818:Animals; D000830:Animals, Laboratory / Q000502:physiology*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D051379:Mice; D009994:Osmolar Concentration; D011188:Potassium / Q000652:urine; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011786:Quality Control; D012964:Sodium / Q000652:urine
D008694:Methamphetamine; D003577:Cytochrome P-450 Enzyme System; D012964:Sodium; C005157:methoxyphenamine; D011188:Potassium