Transplacental distribution of weak acids in mice: accumulation in compartments of high pH.
The transplacental distribution of three weak acids was measured in mice on gestational day 11. The ratio of drug concentration in maternal, embryonic, and extraembryonic compartments compared to maternal plasma followed a consistent hierarchy such that amniotic fluid greater than or equal to exocoelomic fluid greater than embryo greater than embryo plasma greater than maternal skeletal muscle. This distribution pattern correlates well with pH in these compartments and suggests that pH gradients between compartments are an influential factor in determining weak acid drug disposition during pregnancy.
Srivastava
M
M
Children's Hospital Research Foundation, Cincinnati, Ohio 45229.
Collins
M D
MD
Scott
W J
WJ
Wittfoht
W
W
Nau
H
H
D000143:Acids / Q000493:pharmacokinetics*; D000818:Animals; D004114:Dimethadione / Q000493:pharmacokinetics; D005260:Female; D005865:Gestational Age; D006863:Hydrogen-Ion Concentration; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D014018:Tissue Distribution; D014635:Valproic Acid / Q000493:pharmacokinetics
D000143:Acids; D014635:Valproic Acid; D004114:Dimethadione