Byerly M J, DeVane C L
Department of Psychiatry University of Florida College of Medicine, Gainesville 32610-0256, USA.
J Clin Psychopharmacol. 1996 Apr;16(2):177-87. doi: 10.1097/00004714-199604000-00010.
The current literature describing the pharmacokinetics of the atypical antipsychotics clozapine and risperidone is reviewed, and discussion on the clinical significance of these data is presented. These drugs are well absorbed when taken orally but are poorly bioavailable because of presystemic elimination. They are highly cleared by hepatic metabolism involving specific P450 isozymes. Risperidone elimination produces a potent active metabolite. Neither of the drugs has received extensive study related to drug-drug interactions, but several are potentially important because a purported therapeutic plasma concentration range is proposed for clozapine and a possible curvilinear dose response relationship has been reported for risperidone. The current clinical pharmacokinetic database for these atypical antipsychotics suggests that much can be learned with additional study that would be of value in individualizing their dosage regimens.
本文综述了描述非典型抗精神病药物氯氮平和利培酮药代动力学的现有文献，并对这些数据的临床意义进行了讨论。这些药物口服后吸收良好，但由于首过消除，生物利用度较差。它们通过涉及特定P450同工酶的肝脏代谢被高度清除。利培酮消除会产生一种强效活性代谢物。这两种药物均未针对药物相互作用进行广泛研究，但有几种可能具有重要意义，因为氯氮平提出了所谓的治疗血浆浓度范围，而利培酮则报告了可能的曲线剂量反应关系。目前这些非典型抗精神病药物的临床药代动力学数据库表明，通过进一步研究可以了解到很多信息，这对于个体化给药方案具有重要价值。
