Chemical urolithiasis. III. Pharmacokinetics and transplacental transport of terephthalic acid in Fischer-344 rats.
The pharmacokinetics of [14C]terephthalic acid ([14C]TPA) were determined in Fischer-344 rats after intravenous and oral administration. After iv injection, the plasma concentration-time data were fitted using a three-compartment pharmacokinetic model. The average terminal half-life in three rats was 1.2 +/- 0.4 hr, and the average volume of distribution in the terminal phase was 1.3 +/- 0.3 liters/kg. Following administration by gavage, a longer terminal half-life was obtained, indicating that dissolution of [14C]TPA or absorption from the gut may be partially rate-limiting. Recovery of [14C]TPA in the urine following a bolus iv dose was 101 +/- 8%, indicating essentially complete urinary excretion of the compound. No evidence of metabolism of [14C]TPA was obtained by analysis of urine by high-performance liquid chromatography. [14C]TPA was transported to the fetus after administration of the compound to pregnant rats; however, the concentrations in fetal tissues were low relative to the corresponding maternal tissues. Neonatal rats exposed to 5% TPA in the diet of their dams did not develop calculi until the onset of self-feeding. These results demonstrate that TPA is rapidly excreted into urine after administration to rats, and that excretory mechanisms in the dam provide an effective mechanism of defense against TPA-induced urolithiasis in neonatal rats.
D000818:Animals; D005260:Female; D006207:Half-Life; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D010795:Phthalic Acids / Q000378:metabolism* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D001744:Urinary Bladder Calculi / Q000139:chemically induced*
D010795:Phthalic Acids; C011363:terephthalic acid