A study of the disposition of alpha‐methyldopa in newborn infants following its administration to the mother for the treatment of hypertension during pregnancy.

Abstract

Harrow, Middlesex HAl 3UJ1 The nine infants participating in this study were born to mothers who received continuous therapy with a-methyldopa (0.75-2.0 g/day) for several weeks extending to the time of delivery. 2 The concentration of free and total (free plus conjugated) a-methyldopa was determined by gas chromatography-mass spectrometry in amniotic fluid, umbilical cord plasma and maternal plasma at delivery; also in urine collected over timed intervals from neonates during the first days after birth. 3 The results indicate that a-methyldopa administered to the mother is present in the infant at birth at a level comparable to the maternal level and persists for some days. The ratio of conjugated to free drug increases with time after birth. 4 The excretion of free and conjugated a-methyldopa in the urine indicated that the drug is slowly eliminated in the neonate by excretion in the urine and apparently by metabolism, mainly to the sulphate conjugate. 5 The concentration of free and conjugated a-methyldopa in amniotic fluid tended to be higher than in umbilical cord plasma but lower than in neonatal urine, conjugated drug predominated.

Effects of Maternal Alpha Methyldopa Administration on Memory of Rat Offspring during Growing Age

“…AMD can easily pass the placenta and find a measurable level in the fetus [12]. In addition, it can freely access the brain to alleviate the hypertension [19].…”

“…Based on the easily entrance of AMD to the fetus, as well as its ability to affect the cognitive related modulators [9][10][11][12], it seems AMD possesses a capacity to change the behavioral process like memory [13].…”

Pharmacokinetics of Antihypertensive Drugs in the Neonatal Period

“…The specific information on the pharmacokinetics of a-methyldopa in pregnancy and neonates is restricted to three papers [12][13][14]. From the available informa tion, it appears that the drug crosses the pla centa rather rapidly with a ratio between the venous cord plasma and the maternal plasma of 0.70-1.22.…”

“…In the neonate, the drug is cleared very slowly and the computed plasma half-lives are in the order of 10-20 h [12] (against 1-3 h in adults) [11], This may lead to the per sistence of undesired haemodynamic effects for several days after birth.…”

“…In a population of 21 neonates studied so far, 8 had levels over 200 ng/ml 24-120 h after birth [12].…”