MATERNO-FETAL PHARMACOKINETICS AND FETAL DISTRIBUTION OF VALPROIC ACID IN A PREGNANT RHESUS-MONKEY

Google Scholar
  • 1 January 1980
    • journal article
    • research article
    • Vol. 1  (1) , 71-83
Abstract
Chronic indwelling catheters in the maternal femoral artery and vein, fetal carotid artery and jugular vein, and amniotic cavity of a pregnant rhesus monkey permitted administration of the anticonvulsant sodium valproate (NaVPA) and collection of timed samples of maternal and fetal blood and amniotic fluid. After a single i.v. dose (50 mg/kg) to the mother, a rapid distribution phase (t1/2 [half-life] .alpha. = 0.5 min) was followed by a biphasic decline in concentration in maternal blood (t1/2 .beta. = 31 min, t1/2 .gamma. = 380 min). VPA appeared rapidly in fetal blood, reached a concentration slightly higher than in maternal blood by 15 min, and thereafter declined in parallel with the concentration in maternal blood. Terminal fetal/maternal ratios of blood concentration of VPA were .apprx. 1.3. Similar patterns of decline were observed after NaVPA was given i.v. to the fetus. A multicompartment first-order materno-fetal pharmacokinetic model is presented. Tissue distribution studies in the fetus showed that VPA concentration was highest in blood; moderate in heart, liver, lung, spleen, kidney and skeletal muscle; and low in brain.