阿米替林及其主要代谢产物在健康青年人中的药代动力学

PHARMACOKINETICS OF AMITRIPTYLINE IN ADULT VOLUNTEERS WITH CONSIDERATION OF ITS TWO METABOLITES

本文报道8例健康青年志愿者口服50mg阿米替林的药代动力学参数。阿米替林原形药物的药时曲线符合二室线性动力学。其V/F(c)=1231±484 L;t1/2β=41.3±22.3h;t1/2Ka=0.873士0.687h;CL(s)=71.5±41.2 L/h。两种主要代谢产物去甲替林和10-羟基去甲替林的药时曲线符合一室线性动力学。其中去甲替林的药代动力学参数为:t1/2Ke=58.5±34.3h;h1/2Ka=3.20±2.56h;CL(s)=115.4±46.9 L/h。10-羟基去甲替林的药代动力学参数为:t1/2Ke=42.1±23.6h;t1/2Ka=3.57±2.96h;CL(S)=423.7±631.5 L/h。统计学处理发现,两种代谢产物的达峰时间均较原形药物显著延迟,其t1/2Ka也相应延长,峰浓度低于原形药物。同时,代谢产物的MRT显著长于原形药物。本文讨论了代谢产物药代动力学参数的临床意义。

Pharmacokinetic parameters of amitriptyline were studied on eight healthy youngadult volunteers. The concentration-time curve of amitriptyline fitted in with a two-compartment ki-netic model. Its parameters were as follows: V/F(c)=1231±484 L; t1/2β=41.3±22.3h; t1/2Ka=0.873±0.687h; CL_(s)=71. 5±41.2 L/h. The concentration-time curves of the two metabolites, nor-triptyline and 10-hydroxynortriptyline fitted in with one-compartment models. The parameters of nor-triptyline were as follows: t1/2Ke=58.5±34.3h; t1/2Ka=3.20±2.56h; CL_(s)=115.4±46.9 L/h.The parameters of 10-hydroxynortriptyline were as follows: t1/2Ke=42.1±23.6h; t1/2Ka=3.57±2.96h; CL_(s) 423.7±631.5 L/h. it was discovered that the T_(peak) of the two metabolites were significant-ly longer than that of amitriptyline. Their t1/2Ka were correspondingly longer and the c_(max) were lower.The MRT of metabolites were longer than that of the parent drug. The clinical significance of thepharmacokinetics of the metabolites was discussed.