Effect of pregnancy on hepatic microsomal drug metabolism in rabbits and rats

Abstract

In Dutch-belted rabbits, pregnancy caused several-fold decrease of in vitro hepatic microsomal aminopyrine, benzphetamine, and hexobarbital biotransformations. In pregnant Sprague-Dawley rats, various kinds of expressing the in vitro rates of hexobarbital biotransformation (per mg of microsomal protein, g of liver, 100 g of body weight) indicated unchanged or slightly elevated microsomal enzyme activity. In vivo, the course of hexobarbital blood levels after i.p. hexobarbital sodium, 100 mg/kg, indicated that the fate of hexobarbital was not primarily determined by the small changes of microsomal enzyme activity but, rather, by changed hexobarbital distribution. Different ways of expressing in vitro rates of aniline biotransformation showed decreased or unchanged enzyme activity during pregnancy and in vivo experiments indicated that these changes did not affect aniline metabolism in living rats. The results pointed out marked species differences in the effect of pregnancy on drug metabolism. Interpretation of in vitro biotransformation data for living animals suggested that with different substrates, microsomal enzyme activity and distribution, respectively, may exert different effects playing either significant or apparently minor role in drug disposition.

Biotransformation and urinary excretion of 4‐substituted amphetamines in pregnant mice

“…[12][13][14][15] Amphetamines readily cross the placenta; l6 this can result in increased uterine contractility, placental vasoconstriction, and reduced blood supply to the developing foetus. l 7 4-Methoxyamphetamine (PMA, Figure 1) is a potent hallucinogenla and its metabolism may be species specific.19 N-oxidation and oxidative deamination products of PMA were identified from rat liver preparations.% O-demethylation to give 4-hydroxyamphetamine (PHA) is a major metabolic pathway in rat,21 dog, monkey, guinea pig, and human,19 and in a microbial model of mammalian metabolism. 22 There are interspecies differences in the extent of PHA conjugation.…”

Hepatic Drug Metabolism in Pregnancy

“…Similarly a study in [8][9][10][11][12][13][14] week pregnant women with oral metronidazole, which is largely oxidised by the liver, failed to show any differences in elimination from that recorded in non-pregnant women /63/.…”

Influence of Pregnancy on the Hepatic Metabolism of Parathion

“…These findings are supported by numerous in vitro investigations. Dean and Stock [1975] and Gut et al [1976] demonstrated reduced aminopyrine metabo lism during pregnancy in rabbits and rats. In addition, several investigators have demonstrated reductions in benzphetamine-and ethylmorphine-Ndemethylase activities in mice and rats, respectively [Vodicnik et al, 1980;Turcan et al, 1981;Symons et al, 1982].…”