Nonlinear disposition of lithium in rats and saturation of its tubular reabsorption by the sodium-phosphate cotransporter as a cause
Nonlinear disposition of lithium in rats and saturation of its tubular reabsorption by the sodium-phosphate cotransporter as a cause
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DOI：
10.1002/bdd.2116
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发表时间：
2018-02-01
影响因子：
2.1
通讯作者：
Nabekura, Tomohiro
中科院分区：
文献类型：
--
作者：
Uwai, Yuichi;Kawasaki, Tatsuya;Nabekura, Tomohiro
我们之前报道了磷酸钠共转运体对大鼠锂管重吸收的贡献。在本研究中，研究了大鼠肾处理锂的剂量依赖性。当静脉注射1.25mg/kg、2.5mg/kg和25mg/kg氯锂时，计算出60min前锂血药浓度-时间曲线下面积分别为6.23mEqmin/l、8.77mEqmin/l和64.6mEqmin/l。随着给药剂量的增加，锂的肾脏清除率和其部分排泄增加。在1.25mg/kg组（r = 0.840）和2.5mg/kg组（r = 0.773），锂的肾清除率与磷酸盐的尿排泄率密切相关，而在25mg/kg组（r = 0.306），这种相关性较弱。磷酸钠共转运体抑制剂氟膦酸钠（foscarnet）的输注降低了给药2.5mg/kg氯化锂的大鼠对锂的部分重吸收，但对给药25mg/kg的大鼠没有影响。这些结果表明，锂在大鼠肾脏排泄的非线性，与锂再吸收饱和的钠-磷酸钠共转运体可能参与。
We previously reported the contribution of sodium-phosphate cotransporter to the tubular reabsorption of lithium in rats. In the present study, the dose dependency of the renal handling of lithium was examined in rats. When lithium chloride at 1.25mg/kg, 2.5mg/kg and 25mg/kg was intravenously injected as a bolus, the areas under the plasma concentration-time curve of lithium until 60minutes were calculated to be 6.23mEqmin/l, 8.77mEqmin/l and 64.6mEqmin/l, respectively. The renal clearance of lithium and its fractional excretion increased with increments in the dose administered. The renal clearance of lithium strongly correlated with the urinary excretion rate of phosphate in the 1.25mg/kg group (r = 0.840) and 2.5mg/kg group (r = 0.773), whereas this correlation was weak in the 25mg/kg group (r = 0.306). The infusion of foscarnet, a typical inhibitor of sodium-phosphate cotransporter, decreased the fractional reabsorption of lithium in rats administered lithium chloride at 2.5mg/kg, but did not affect it in rats administered 25mg/kg. These results demonstrate the nonlinearity of the renal excretion of lithium in rats, with the saturation of lithium reabsorption by the sodium-phosphate cotransporter potentially being involved.