A comparison of morphine and methadone disposition in the maternal-fetal unit

American Journal of Obstetrics and Gynecology
H H SzetoJ W McFarland

Abstract

The extent of fetal exposure to a drug is a function of placental and fetal clearances of the drug. We have compared the placental and fetal clearances of morphine and methadone under steady-state conditions in the chronic pregnant ewe preparation. Morphine and methadone were infused at constant rates to the mother and fetus, and steady-state maternal and fetal plasma concentrations of the drugs were determined by radioimmunoassay. At steady state after maternal infusion of the drugs, the maternal: fetal free drug concentration ratios were 7.6 +/- 0.6 for morphine and 2.9 +/- 0.6 for methadone. The clearance of morphine from mother to fetus (24.9 +/- 3.0 ml/min) was fifteenfold less than that of methadone (390.3 +/- 92.8 ml/min). Fetal nonplacental clearance of methadone (381 +/- 89.1 ml/min) was higher than that of morphine (125.6 +/- 15.3 ml/min). Fetal clearance accounted for 67.4 +/- 3.9% of total morphine clearance from the fetal compartment, but only 42.8 +/- 4.9% of total methadone clearance. Fetal clearance of methadone increases with age in the early third trimester. The lower extent of fetal exposure to morphine compared to methadone is due primarily to a slower clearance of morphine across the placenta from mother to...Continue Reading

Citations

Jan 1, 1990·Journal of Perinatal Medicine·E GerdinB Lindberg
Mar 1, 1990·Pharmacology & Toxicology·E GerdinA Rane
Apr 25, 2001·Journal of Addictive Diseases·E T MoolchanD Epstein
Apr 25, 2007·Journal of Psychosomatic Obstetrics and Gynaecology·Maki KashiwagiUlrike Ehlert
Jun 21, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Marianne GarlandRaymond I Stark
Nov 1, 2011·Critical Reviews in Clinical Laboratory Sciences·Bhushan M KapurPeter Selby
Jul 9, 2008·Journal of Psychosomatic Obstetrics and Gynaecology·Maki KashiwagiUlrike Ehlert
Jul 17, 1998·Pediatric Research·Marianne GarlandRaymond I Stark
Jun 2, 2007·Expert Opinion on Drug Metabolism & Toxicology·Päivi MyllynenKirsi Vähäkangas
Oct 21, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Marianne GarlandRaymond I Stark
Aug 1, 1997·Therapeutic Drug Monitoring·G Skopp, L Pötsch
Jan 1, 1989·Annals of the New York Academy of Sciences·H H Szeto

Related Concepts

Metazoa
Fetal Structures
Gestational Age
Maternal-Fetal Exchange
Total Body Clearance Rate
Physeptone
Morphine Sulfate (2: 1), Pentahydrate
Placenta
Plasma Protein Binding Capacity
Dall Sheep

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