O'Neill P J, Yorgey K A, McKown L A
J Pharmacol Exp Ther. 1981 Dec;219(3):665-8.
The pharmacokinetics and renal handling of zomepirac, a new analgesic agent, were studied in rhesus monkeys. Single oral 5, 10 and 40 mg/kg doses were administered to fasted male and female rhesus monkeys. After the 40 mg/kg dose, about 2.5-fold higher peak zomepirac plasma concentrations and area under the curve were observed that predicted from the lower doses and plasma clearance decreased from 4.6 to 1.8 ml/min/kg. Because zomepirac is a weak acid and is a substrate for the renal tubular acid transport system, the possible role of concentration-dependent renal clearance was evaluated. Renal clearance of zomepirac averted only 0.007 ml/min/kg and was concentration independent. Essentially all of the plasma clearance was accounted for by formation of the glucuronide conjugate of zomepirac, which was subsequently excreted in the urine. These findings, when placed in perspective with other data, indicate that the nonlinear kinetics of zomepirac in fasted rhesus monkeys are probably due to saturation of metabolism.
在恒河猴身上研究了一种新型镇痛药佐美酸的药代动力学和肾脏处理情况。给禁食的雄性和雌性恒河猴单次口服5、10和40毫克/千克剂量的佐美酸。给予40毫克/千克剂量后，观察到佐美酸的血浆峰值浓度和曲线下面积比根据较低剂量预测的值高出约2.5倍，血浆清除率从4.6毫升/分钟/千克降至1.8毫升/分钟/千克。由于佐美酸是一种弱酸，是肾小管酸转运系统的底物，因此评估了浓度依赖性肾脏清除的可能作用。佐美酸的肾脏清除率仅为0.007毫升/分钟/千克，且与浓度无关。基本上所有的血浆清除都是由佐美酸的葡萄糖醛酸结合物的形成所致，该结合物随后经尿液排出。将这些发现与其他数据综合来看，表明禁食的恒河猴中佐美酸的非线性动力学可能是由于代谢饱和所致。
