Strolin Benedetti M, Whomsley R, Mathy F-X, Jacques P, Espie P, Canning M
Non Clinical Development Department, UCB Pharma S.A., 21 rue de Neuilly, 92000 Nanterre, France.
Fundam Clin Pharmacol. 2008 Feb;22(1):19-23. doi: 10.1111/j.1472-8206.2007.00543.x. Epub 2007 Nov 15.
Competition for uptake and/or efflux transporters can be responsible for drug interactions. Cetirizine is mainly eliminated unchanged in urine through both glomerular filtration and tubular secretion. The aim of this study was to investigate whether the eutomer, levocetirizine, and the distomer, dextrocetirizine, have a similar tubular secretion. The renal clearance associated with tubular secretion was calculated from the renal clearance of levocetirizine and dextrocetirizine obtained in a study in healthy volunteers. The values of the unbound fraction in plasma were obtained in an in vitro study of the binding of (14)C-cetirizine and (14)C-levocetirizine to human plasma proteins using equilibrium dialysis and chiral high-performance liquid chromatography (HPLC) with on-line liquid scintillation counting. The unbound fraction was 0.074 for levocetirizine and 0.141 for dextrocetirizine. The tubular secretion of dextrocetirizine (44.5 mL/min) is higher than that of levocetirizine (23.1 mL/min), which may have consequences for drug interactions at the renal level. The higher tubular secretion for dextrocetirizine may be due to the higher free fraction available for secretion or to a higher affinity for (a) renal transporter(s) mediating the secretion pathway.
对摄取和/或外排转运体的竞争可能导致药物相互作用。西替利嗪主要通过肾小球滤过和肾小管分泌以原形经尿液排出。本研究的目的是调查优映体左西替利嗪和对映体右西替利嗪是否具有相似的肾小管分泌情况。在一项针对健康志愿者的研究中，根据所获得的左西替利嗪和右西替利嗪的肾清除率计算与肾小管分泌相关的肾清除率。血浆中游离分数的值是通过使用平衡透析和在线液体闪烁计数的手性高效液相色谱法（HPLC）对（14）C - 西替利嗪和（14）C - 左西替利嗪与人血浆蛋白结合进行体外研究获得的。左西替利嗪的游离分数为0.074，右西替利嗪为0.141。右西替利嗪的肾小管分泌（44.5 mL/分钟）高于左西替利嗪（23.1 mL/分钟），这可能会对肾脏水平的药物相互作用产生影响。右西替利嗪较高的肾小管分泌可能是由于可供分泌的游离部分较高，或者是对介导分泌途径的肾转运体具有更高的亲和力。
