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.

中文翻译：

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化学尿石症。三，对苯二甲酸在Fischer-344大鼠中的药代动力学和胎盘运输。

在静脉和口服给药后，在Fischer-344大鼠中测定[14C]对苯二甲酸（[14C] TPA）的药代动力学。静脉注射后，使用三室药代动力学模型拟合血浆浓度-时间数据。三只大鼠的平均终末半衰期为1.2 +/- 0.4小时，终末期的平均分布体积为1.3 +/- 0.3升/千克。通过管饲法给药后，获得了更长的终末半衰期，表明[14C] TPA的溶解或从肠道的吸收可能是部分限速的。静脉推注后尿液中[14C] TPA的回收率为101 +/- 8％，表明该化合物的尿排泄基本完全。通过高效液相色谱法分析尿液，未获得[14C] TPA代谢的证据。[14C] TPA在给妊娠大鼠服用该化合物后被转运至胎儿；但是，相对于相应的母体组织，胎儿组织中的浓度较低。在母鼠的饮食中暴露于5％TPA的新生大鼠直到自食开始才出现结石。这些结果表明，向大鼠给药后，TPA迅速排泄到尿液中，并且大坝中的排泄机制为防御TPA诱导的新生大鼠尿路结石症提供了有效的机制。