Janicak P G
Research Unit, Illinois State Psychiatric Institute, Chicago 60651.
J Clin Psychiatry. 1993 Sep;54 Suppl:35-41; discussion 55-6.
This review considers the relevance of clinical pharmacokinetics and the role of therapeutic drug monitoring (TDM) for two classes of psychotropics: the anticonvulsant mood stabilizers and the antipsychotics. In the first class, carbamazepine is a potent stimulator of the hepatic microsomal enzyme oxidation system, while valproic acid inhibits these same enzymes. In addition, these agents' highly protein-bound status can alter the availability of the free fraction of other coadministered agents. For both reasons, TDM during their administration may be useful. The antipsychotics demonstrate wide variations in absorption, first-pass effect, and volume of distribution among individuals. Depot antipsychotics have long elimination half-lives, often taking months to achieve steady-state levels or, conversely, to complete their washout. While correlations between antipsychotic plasma concentrations and clinical response are still under study, there are specific instances when TDM can be used to maximize clinical benefit and/or avoid adverse events.
本综述探讨了临床药代动力学的相关性以及治疗药物监测(TDM)在两类精神药物中的作用:抗惊厥情绪稳定剂和抗精神病药物。在第一类药物中,卡马西平是肝微粒体酶氧化系统的强效刺激剂,而丙戊酸则抑制这些相同的酶。此外,这些药物高度的蛋白结合状态可改变其他同时使用药物的游离部分的可用性。由于这两个原因,在它们给药期间进行TDM可能是有用的。抗精神病药物在个体间的吸收、首过效应和分布容积方面表现出很大差异。长效抗精神病药物的消除半衰期很长,通常需要数月才能达到稳态水平,或者相反,才能完成清除。虽然抗精神病药物血浆浓度与临床反应之间的相关性仍在研究中,但在某些特定情况下,TDM可用于使临床获益最大化和/或避免不良事件。