A Determination Of The Placental Permeability Of Morphine-3-Glucuronide In Guinea Pigs Using High Pressure Liquid Chromatography With Ultra-Violet Detection

Abstract

Morphine (M) is conjugated to glucuronic acid in the fetus. This metabolite, morphine-3-glucuronide (M3G), is less lipid soluble and larger than M. Because of the potential for fetal accumulation (1) and toxicity (2) the permeability for M3G was examined in the guinea pig which, like the human, has a hemomonochorial placenta. Seven dams in the last half of gestation and 30 fetuses were studied. A carotid artery catheter was placed in the anesthetized dam. Two hours later, M3G was injected into the catheter of the awake animal and maternal samples were taken at intervals for 30 minutes. The dam was re-anesthetized and fetal samples taken from the umbilical vein. Plasma M3G was determined by High Pressure Liquid Chromatography (HPLC). Using Fick's law of diffusion, the permeability surface area product (P.S.) per gram placental weight was calculated to be 3.1 X 10'5± 0.3 ml sec '1 g'1 (mean ± S.E.). PS increased with increasing fetal weight. Although the placenta becomes more permeable to M3G as gestation progresses, the permeability of this hydrophilic metabolite is restricted as term approaches and therefore M3G would accumulate in the fetus during chronic morphine exposure, due to conjugation of fetal M to M3G.