Lam Y W, Boyd R A, Chin S K, Chang D, Giacomini K M
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7765.
J Clin Pharmacol. 1991 May;31(5):429-32. doi: 10.1002/j.1552-4604.1991.tb01898.x.
Renal tubular transport of organic anions and cations is assumed to be mutually exclusive. However, results of a number of in vitro and in vivo studies suggest an interaction between the organic anion, probenecid, and various organic cations in the proximal renal tubule. To evaluate the clinical importance of such an interaction, the authors investigated the pharmacokinetics and pharmacodynamics of procainamide, an organic cation with a low therapeutic index that is excreted in part by active secretion in the proximal tubule, in the presence and absence of probenecid. In a randomized crossover study, six healthy subjects received a single 750-mg IV dose of procainamide, with and without prior probenecid administration (2 g orally). Blood and urine samples were obtained and pharmacokinetic parameters of procainamide were determined in each treatment period. QT intervals were measured from ECG recordings that were obtained at blood collection times for pharmacodynamic evaluation. Coadministration of probenecid did not result in any significant change in the overall disposition of procainamide. In particular, renal clearance was not significantly different (488 +/- 95 mL/min without probenecid vs. 478 +/- 69 mL/min in the presence of probenecid). Our data suggest an interaction between probenecid and procainamide in the proximal renal tubule does not exit. Reasons for this lack of interaction are discussed.
肾小管对有机阴离子和阳离子的转运被认为是相互排斥的。然而，一些体外和体内研究结果表明，有机阴离子丙磺舒与近端肾小管中的各种有机阳离子之间存在相互作用。为了评估这种相互作用的临床重要性，作者研究了在有和没有丙磺舒存在的情况下，普鲁卡因胺（一种治疗指数较低的有机阳离子，部分通过近端小管的主动分泌排泄）的药代动力学和药效学。在一项随机交叉研究中，六名健康受试者接受了单次750毫克静脉注射剂量的普鲁卡因胺，分别在服用和未服用丙磺舒（口服2克）之前。采集血液和尿液样本，并在每个治疗期测定普鲁卡因胺的药代动力学参数。从采血时获得的心电图记录中测量QT间期，用于药效学评估。丙磺舒的共同给药并未导致普鲁卡因胺的总体处置发生任何显著变化。特别是，肾脏清除率没有显著差异（未服用丙磺舒时为488±95毫升/分钟，服用丙磺舒时为478±69毫升/分钟）。我们的数据表明，丙磺舒与近端肾小管中的普鲁卡因胺之间不存在相互作用。讨论了这种缺乏相互作用的原因。
