Kotaki H, Hori S, Saitoh Y, Nakagawa F, Tamura Z
J Pharmacobiodyn. 1986 Dec;9(12):970-4.
Three types of rats with respect to sensitivity to clioquinol have been identified, the highly sensitive (S-rat), the intermediately sensitive, and the resistant (R-rat). In a toxicity test that lasted for 20 d after birth, the difference in sensitivity to clioquinol between S- and R-rats was confirmed by repeated subcutaneous administration of a clioquinol suspension prepared with polysorbate 80 (clioquinol dose of 150 or 300 mg/kg/d). Plasma and tissue concentrations of clioquinol and the rate of metabolism of the drug in neonatal S- and R-rats were measured. Plasma concentration of clioquinol in 1-d-old S-rats after a single subcutaneous administration was higher than that in the same age R-rats and the area under the mean plasma concentration-time curve for the S-rats was approximately twice that for the R-rats. In addition, clioquinol concentrations in liver, kidney and brain of S-rats at 9 h after the administration were more than twice those of the R-rats. From the experiments on the formation of clioquinol glucuronide and sulfate with 9000 g supernatant fraction of liver, it was suggested that the difference in the plasma concentration after the administration may be responsible for the difference in the metabolizing rate of clioquinol.
已鉴定出对氯碘羟喹敏感性不同的三种类型大鼠，即高敏型（S型大鼠）、中度敏感型和抗性型（R型大鼠）。在出生后持续20天的毒性试验中，通过反复皮下注射用聚山梨酯80配制的氯碘羟喹悬浮液（氯碘羟喹剂量为150或300mg/kg/天），证实了S型和R型大鼠对氯碘羟喹的敏感性差异。测定了新生S型和R型大鼠体内氯碘羟喹的血浆和组织浓度以及药物代谢率。单次皮下给药后，1日龄S型大鼠的氯碘羟喹血浆浓度高于同龄R型大鼠，S型大鼠平均血浆浓度-时间曲线下面积约为R型大鼠的两倍。此外，给药后9小时，S型大鼠肝脏、肾脏和大脑中的氯碘羟喹浓度是R型大鼠的两倍多。通过用肝脏9000g上清液部分进行氯碘羟喹葡萄糖醛酸苷和硫酸盐形成实验表明，给药后血浆浓度的差异可能是氯碘羟喹代谢率差异的原因。
