Pharmacokinetic Examination of p-Aminobenzoic Acid Passage through the Placenta and the Small Intestine in Rats

• Published in: Journal of drug targeting 1997, Vol.5 (1), p.57-65
• Main Authors: Štaud, F., Fendrich, Z., Jindrová, O., Lázní ek, M.
• Format: Article
• Language: English
• Subjects: 4-Aminobenzoic Acid - administration & dosage; 4-Aminobenzoic Acid - pharmacokinetics; Analgesics; Animals; Biological and medical sciences; drug absorption; Duodenum - metabolism; Female; Injections, Intravenous; Intestinal Absorption - physiology; Intestine, Small - metabolism; Intubation, Gastrointestinal; Medical sciences; Neuropharmacology; p-aminobenzoic acid; PABA; pharmacokinetics; Pharmacology. Drug treatments; Placenta - metabolism; Placental transfer; Pregnancy; Protein Binding; rat; Rats; Rats, Wistar; Skin, nail, hair, dermoskeleton
• ISSN: 1061-186X; 1029-2330
• DOI: 10.3109/10611869708995858

Abstract 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 (keqilibration = 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 1/kg); however, Vd of AP in pregnant animals was estimated to be 1.81 1/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.