Morphine metabolism in the pregnant guinea pig and her pups

The study of chronic in utero exposure to heroin and morphine in the human is limited by polysubstance abuse. The guinea pig was used as a model for t he human to determine the in vivo and in vitro effect of chronic morphine e xposure on morphine metabolism in the pregnant dam and her offspring. In vi vo pharmacokinetics of morphine were examined in pregnant guinea pigs follo wing pretreatment with either saline or morphine. In vitro hepatic enzyme k inetics were also examined in a similar group of pregnant dams and their fe tuses. Additional pregnant dams were allowed to give birth and their pups' enzyme kinetics were studied at 1, 3, and 7 days. Apparent V-MAX for the fo rmation of both morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6 G) formation was significantly increased in the morphine-treated pregnant g uinea pig. However, no effect of morphine treatment was detectable on the i n vivo pharmacokinetics of morphine in the pregnant dam. The apparent morph ine K-M for the formation of M3G was significantly different than the appar ent K-M for the formation of M6G. Significant age effects on the enzyme kin etics were found. The apparent V-MAX for the formation of both glucuronides increased through the neonatal period. Through literature comparisons, the guinea pig was shown to have in vivo pharmacokinetics similar to the pregn ant human, and the guinea pig pups were found to have enzyme development co nsistent with in vive pharmacokinetic development seen in human neonates, i nfants and children. Copyright (C) 1999 S. Karger AG. Basel.