Neonatology

Original Paper

Morphine Metabolism in the Pregnant Guinea Pig and Her Pups

Smith S.A.b · Woolsey J.B.a · Olsen G.D.a,b

Author affiliations

Departments of aPhysiology and Pharmacology, and bPediatrics, School of Medicine, Oregon Health Sciences University, Portland, Oreg., USA

Keywords: Morphine-6-glucuronideMorphine-3-glucuronideChronic morphine exposureDevelopmental pharmacokineticsMorphine pharmacokinetics

Related Articles for ""
Biol Neonate 1999;76:362–373
https://doi.org/10.1159/000014180

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: November 10, 1999
Issue release date: December 1999

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 5

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

Abstract

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.

© 1999 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: November 10, 1999
Issue release date: December 1999

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 5

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

Copyright / Drug Dosage / Disclaimer

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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1999, Vol.76, No. 6

December 1999

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