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目的S(+)-盐酸氯胺酮是盐酸氯胺酮右旋光学异构体,研究大鼠静脉注射给药后体内血浆药动学、组织分布、代谢及排泄特征,为临床应用提供参考依据。方法本实验采用LC-MS测定生物样品中S(+)-盐酸氯胺酮浓度。结果大鼠静脉注射不同剂量S(+)-盐酸氯胺酮(6.25,12.5,25mg·kg-1)后,ρmax及AUC与给药剂量呈正相关;体内分布以肾、肾上腺最高,脑、小肠、肌肉、胃、心脏等次之,肝、肺等组织水平最低。S(+)-盐酸氯胺酮静脉注射后经粪、尿、胆汁排泄,排泄量分别占给药量的0.007%,0.66%,和16%。S(+)-盐酸氯胺酮在大鼠体内可经CYP2E1,CYP3A和CYP2C同工酶代谢,氧化成去甲基代谢物和双键去甲基代谢物。结论研究S(+)-盐酸氯胺酮的血浆药动学、组织分布、代谢及排泄特征可为该药临床应用的安全性和有效性提供重要的参考依据。
Objective S (+) - ketamine hydrochloride is a dextrorotatory optical isomer of ketamine hydrochloride, and studies the pharmacokinetics, tissue distribution, metabolism and excretion of rat plasma after intravenous injection, providing a reference for clinical application. Methods In this study, the concentration of S (+) - ketamine hydrochloride in biological samples was determined by LC-MS. Results After administration of different concentrations of S (+) - ketamine hydrochloride (6.25,12.5,25 mg · kg -1), there was a positive correlation between ρmax and AUC and the dose of administration. The distribution in the body was highest in kidney, adrenal gland, brain, small intestine and muscle , Stomach, heart and other times, liver, lung and other organizations the lowest level. Excretion and excretion of feces, urine and bile were accounted for 0.007%, 0.66%, and 16% respectively after administration of S (+) - ketamine hydrochloride intravenously. S (+) - ketamine hydrochloride can be metabolized by CYP2E1, CYP3A and CYP2C isozymes in rats to oxidative demethylation and double bond demethylation. Conclusion The study of plasma pharmacokinetics, tissue distribution, metabolism and excretion of S (+) - ketamine hydrochloride may provide important reference for the safety and efficacy of this drug.