Pharmacokinetic examination of p-aminobenzoic acid passage through the placenta and the small intestine in rats.
In the present study the permeability of the rat small intestine and the placenta to p-aminobenzoic acid (PABA) and antipyrine (AP) was investigated. Perfusion of the rat term placenta was used to determine the materno-fetal transfer of both compounds. PABA appeared in the fetal compartment faster than AP (ktransfer = 0.064 and 0.046 min-1, respectively). The rate of equilibration between the maternal and fetal compartments and placental clearance were lower for PABA than for AP (kequilibration = 0.011 and 0.020 min-1; Clp = 0.22 and 0.33 ml/min, respectively); the feto-maternal concentration ratios at equilibrium (FMCReq) were, however, mutually comparable. Similarly, PABA proved to be absorbed from the small intestine significantly faster than AP (ka = 0.824 min-1 and 0.479 min-1; tmax = 3.1 min and 8.9 min, respectively). The apparent volume of distribution (Vd) of AP in non-pregnant animals showed that the drug is distributed into the whole body water as expected (Vd = 0.66 l/kg); however, Vd of AP in pregnant animals was estimated to be 1.81 l/kg. Vd of PABA in non-pregnant animals showed its partially limited distribution, which was only slightly increased in the pregnant animals. Our results confirmed a faster penetration of hydrophilic PABA across the placenta and the small intestine than that of lipophilic AP. The mechanism of transplacental passage of PABA, however, remains to be determined.
Staud
F
F
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
Fendrich
Z
Z
Jindrová
O
O
Láznícek
M
M
D010129:4-Aminobenzoic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D004386:Duodenum / Q000378:metabolism; D005260:Female; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism*; D007441:Intubation, Gastrointestinal; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
D010129:4-Aminobenzoic Acid