实验性肾衰竭对犬托芬那酸处置的影响。

The effect of experimental renal failure on tolfenamic acid disposition in the dog.

作者信息

Lefebvre H P, Laroute V, Alvinerie M, Schneider M, Vinclair P, Braun J P, Toutain P L

机构信息

Unité INRA de Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire, Toulouse, France.

出版信息

Biopharm Drug Dispos. 1997 Jan;18(1):79-91. doi: 10.1002/(sici)1099-081x(199701)18:1<79::aid-bdd34>3.0.co;2-f.

DOI:10.1002/(sici)1099-081x(199701)18:1<79::aid-bdd34>3.0.co;2-f

PMID:9008271

Abstract

The pharmacokinetic disposition of tolfenamic acid, an NSAID, after a single administration of tolfenamic acid (4 mg kg(-1)) by the intravenous (IV) route was compared in eight dogs before and after a surgically induced renal failure. Renal impairment was confirmed by a significant increase (p <0.001) of water intake, urine volume, and urea and creatinine plasma concentration. PAH and inulin clearances decreased after surgery from 15.2 +/- 4.2 to 9.5 +/- 0.8 mL kg(-1) min(-1) (p < 0.05) and from 4.37 +/- 1.15 to 2.43 +/- 0.88 mL kg(-1) min(-1) (p=0.067),respectively. After surgery, clearance of TA was significantly (p <0.001) increased, from 2.22 +/- 1.68 to 3.59 +/- 1.81 mL kg (-1) min(-1). There was no modification of the steady-state volume of distribution (p > 0.05) and the mean residence time was significantly decreased from 606 +/- 199 to 373 +/- 302 min (p < 0.05). No variation of binding to plasma proteins (> or = 99%) was observed. These results suggest that renal insufficiency could increase hepatic metabolism and/or alter the enterohepatic cycle of TA.

摘要

通过静脉注射（IV）途径单次给予托芬那酸（4 mg kg⁻¹）后，比较了8只犬在手术诱导肾衰竭前后非甾体抗炎药托芬那酸的药代动力学特征。通过水摄入量、尿量以及尿素和肌酐血浆浓度显著增加（p < 0.001）来确认肾功能损害。手术后，对氨基马尿酸（PAH）清除率和菊粉清除率分别从15.2 ± 4.2降至9.5 ± 0.8 mL kg⁻¹ min⁻¹（p < 0.05）和从4.37 ± 1.15降至2.43 ± 0.88 mL kg⁻¹ min⁻¹（p = 0.067）。手术后，托芬那酸的清除率显著增加（p < 0.001），从2.22 ± 1.68升至3.59 ± 1.81 mL kg⁻¹ min⁻¹。稳态分布容积没有改变（p > 0.05），平均驻留时间从606 ± 199显著降至373 ± 302分钟（p < 0.05）。未观察到与血浆蛋白结合的变化（≥ 99%）。这些结果表明肾功能不全可能会增加托芬那酸的肝脏代谢和/或改变其肠肝循环。