Morphine metabolism in the pregnant guinea pig and her pups
| Autor: | George D. Olsen, Jeffrey B. Woolsey, Sue Ann Smith |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Offspring Guinea Pigs Pharmacology Guinea pig chemistry.chemical_compound Pharmacokinetics In vivo Pregnancy Internal medicine medicine Animals Maternal-Fetal Exchange reproductive and urinary physiology Morphine-3-glucuronide Morphine Derivatives Morphine business.industry Morphine-6-glucuronide Kinetics Endocrinology chemistry In utero Pediatrics Perinatology and Child Health Female business Developmental Biology medicine.drug |
| Zdroj: | Biology of the neonate. 76(6) |
| ISSN: | 0006-3126 |
| Popis: | 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 the human to determine the in vivo and in vitro effect of chronic morphine exposure on morphine metabolism in the pregnant dam and her offspring. In vivo pharmacokinetics of morphine were examined in pregnant guinea pigs following pretreatment with either saline or morphine. In vitro hepatic enzyme kinetics were also examined in a similar group of pregnant dams and their fetuses. Additional pregnant dams were allowed to give birth and their pups’ enzyme kinetics were studied at 1, 3, and 7 days. Apparent VMAX for the formation of both morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) formation was significantly increased in the morphine-treated pregnant guinea pig. However, no effect of morphine treatment was detectable on the in vivo pharmacokinetics of morphine in the pregnant dam. The apparent morphine KM for the formation of M3G was significantly different than the apparent KM for the formation of M6G. Significant age effects on the enzyme kinetics were found. The apparent VMAX 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 pregnant human, and the guinea pig pups were found to have enzyme development consistent with in vivo pharmacokinetic development seen in human neonates, infants and children. |
| Databáze: | OpenAIRE |
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