Disposition of morphine in tissues of the pregnant rat and foetus following single and continuous intraperitoneal administration to the mother

C. L. DeVane, J. W. Simpkins, D. W. Boulton, Steven Laizure, R. L. Miller

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Foetal exposure to maternally administered opiates such as morphine represent a serious human health problem but disposition studies in man are difficult to perform. Morphine disposition was therefore investigated in pregnant rats and their foetuses near term as a model. Disposition was examined either following intraperitoneal dosing as a single dose or continuous infusion. A high-pressure liquid chromatography assay for morphine in plasma and tissue was developed and validated. Following the single morphine dose, foetal distribution was rapid and concentrations in foetal and placental tissue were from 2.6 (whole foetus) to 27.6 (placenta) times higher compared with maternal plasma. The rank order of the area under the concentration vs time curve (AUC) of morphine in tissues was: placenta ≥ foetal liver > foetal brain > whole foetus > maternal brain. The foetal brain to maternal brain AUC ratio for morphine was 9.5, suggesting large differences in their blood-brain barrier permeability. Following continuous administration of morphine there were significant linear relationships between maternal plasma and tissue concentrations with the same rank order as the single dose study. However, following continuous administration the relative amount of morphine in placenta and foetal liver was reduced by half and one-third, respectively, compared with the single dose study. These results document why the rat foetus is particularly susceptible to the pharmacodynamic effects of morphine following maternal administration.

Original languageEnglish (US)
Pages (from-to)1283-1287
Number of pages5
JournalJournal of Pharmacy and Pharmacology
Volume51
Issue number11
DOIs
StatePublished - Jan 1 1999

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Morphine
Fetus
Mothers
Placenta
Brain
Area Under Curve
Opiate Alkaloids
Liver
Blood-Brain Barrier
Permeability
High Pressure Liquid Chromatography
Health

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Disposition of morphine in tissues of the pregnant rat and foetus following single and continuous intraperitoneal administration to the mother. / DeVane, C. L.; Simpkins, J. W.; Boulton, D. W.; Laizure, Steven; Miller, R. L.

In: Journal of Pharmacy and Pharmacology, Vol. 51, No. 11, 01.01.1999, p. 1283-1287.

Research output: Contribution to journalArticle

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