Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
Pharmacology. 2021;106(7-8):446-450. doi: 10.1159/000515934. Epub 2021 May 12.
Lithium, administered to patients of bipolar disorders, is mainly excreted into urine, and tubular reabsorption at the proximal tubule is involved in the renal handling of lithium. In this study, we examined the renal excretion of lithium in rats with Fanconi syndrome, characterized by defects of transports of various compounds at the proximal tubules, induced by maleic acid. After maleic acid was intravenously injected, mannitol and lithium chloride were infused in turn. Using samples of plasma and bladder urine during the mannitol infusion, renal parameters were determined. Pharmacokinetic parameters of lithium were obtained using samples during the lithium chloride infusion. Maleic acid decreased creatinine clearance and increased the fractional excretion of glucose and phosphate, suggesting the induction of Fanconi syndrome. In rats with Fanconi syndrome, plasma concentration of lithium was increased, and its renal clearance was decreased. No effect on the fractional excretion of lithium was exhibited. This study represents that the tubular reabsorption of lithium was impaired to the same degree with glomerular filtration in rats with experimental Fanconi syndrome and that the dysfunction of the tubular reabsorption of glucose and phosphate was more severe. It is possible that Fanconi syndrome inhibited the reabsorption of lithium at the proximal tubule and facilitated the reabsorption of lithium from the loop of Henle to the collecting duct.
锂，用于治疗双相情感障碍患者，主要通过尿液排泄，而近端肾小管的重吸收在肾脏处理锂的过程中起作用。在这项研究中，我们研究了马来酸诱导的范可尼综合征（一种以近端肾小管多种化合物转运缺陷为特征的疾病）大鼠的锂排泄。在静脉注射马来酸后，我们依次给予甘露醇和氯化锂输液。在甘露醇输液期间采集血浆和膀胱尿液样本，测定肾脏参数。在氯化锂输液期间采集样本，获得锂的药代动力学参数。马来酸降低了肌酐清除率，增加了葡萄糖和磷酸盐的分数排泄，表明范可尼综合征的诱导。在范可尼综合征大鼠中，血浆锂浓度增加，肾清除率降低。锂的分数排泄没有影响。本研究表明，在实验性范可尼综合征大鼠中，锂的肾小管重吸收与肾小球滤过程度相同受损，葡萄糖和磷酸盐的肾小管重吸收功能障碍更严重。范可尼综合征可能抑制了近端肾小管对锂的重吸收，促进了从亨利袢升支到集合管对锂的重吸收。
