APPLICATION OF PHARMACOKINETICS TO NEUROTRANSMITTER DISPOSITION

3-甲氧基-4-羟基苯乙二醇在人体内的分布 （MHPG），去甲肾上腺素的主要代谢产物，已被建模。 的 脑脊液MHPG浓度和尿排泄率 在用地昔帕明（地昔帕明）治疗之前和治疗期间， ZIM用于评价药物治疗对 中枢神经系统产生MHPG的速率。 中间价 MHPG的产生减少了45.7 ± 17.4%（P <0.05）， ZIM处理组比对照组提高21.4 ± 17.9%。 一个搅拌良好的肝脏代谢模型已被应用于发表的数据 褪黑激素在人体内的分布 褪黑激素可以被描述为 受肝脏代谢较大首过效应影响物质。 这 首过效应似乎并不能解释所有的不良口腔 褪黑素的生物利用度。 虽然有报道称， 肝硬化患者褪黑素的清除率降低 肝硬化，清除概念的应用相同的数据提供了 证明褪黑激素的内源性产生速率也降低。

The disposition in human patients of 3-methoxy-4-hydroxy phenylglycol (MHPG), a major metabolite of norepinephrine, has been modeled. The cerebrospinal fluid concentration of MHPG and the urinary excretion rates of its metabolites before and during treatment with desipramine (DMI) and zimelidine (ZIM) were used to evaluate the effect of drug treatment upon the central nervous system rate of production of MHPG. The central rate of production of MHPG was decreased (P less than .05) by 45.7 plus/minus 17.4% by DMI treatment and by 21.4 plus/minus 17.9% by ZIM treatment. A well-stirred model of liver metabolism has been applied to published data on the disposition of melatonin in humans. Melatonin can be described as a substance subject to a large first pass effect of hepatic metabolism. This first pass effect does not appear to account for all of the poor oral bioavailability of melatonin. Although it has been reported that the elimination rate of melatonin is decreased in patients with hepatic cirrhosis, the application of clearance concepts to the same data provides evidence that the endogenous production rate of melatonin is also decreased.