Materno-fetal pharmacokinetics and fetal distribution of valproic acid in a pregnant rhesus monkey.
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 sodium valproate (NaVPA) and collection of timed samples of maternal and fetal blood and amniotic fluid. After a single IV dose (50 mg/kg) to the mother, a rapid distribution phase (t1/2 alpha = 0.5 minute) was followed by a biphasic decline in concentration in maternal blood (t1/2 beta = 31 minutes, t1/2 gamma = 390 minutes). VPA appeared rapidly in fetal blood, reached a concentration slightly higher than in maternal blood by 15 minutes, and thereafter declined in parallel with the concentration in maternal blood. Terminal fetal/maternal ratios of blood concentration of VPA were about 1.3. Similar patterns of decline were observed after NaVPA was given IV 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, spleen, kidney, and skeletal muscle; and low in brain.
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007700:Kinetics; D008253:Macaca mulatta; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011485:Protein Binding; D014018:Tissue Distribution; D014635:Valproic Acid / Q000378:metabolism*
D014635:Valproic Acid