Mental Health Research Center, Eastern State Hospital, 627 West Fourth St., Lexington, KY 40508, USA.
Psychosomatics. 2010 Jan-Feb;51(1):80-8. doi: 10.1176/appi.psy.51.1.80.
Several new atypical antipsychotics have become available for use, but knowledge about their pharmacology may not be widespread.
This review aims to increase awareness and knowledge about risperidone (R) and paliperidone (9-hydroxyrisperidone [9-OHR]), their pharmacokinetics, and pharmacodynamics.
The authors present a review of the literature on R and 9-OHR.
Oral R may be approximately twice as potent as oral 9-OHR. Levels of R and 9-OHR in R-treated patients may help clinicians prescribe 9-OHR. In R-treated patients, the R/9-OHR concentration ratio is an index of CYP2D6 activity; an inverted ratio (>1) indicates a CYP2D6 poor metabolizer (PM) or the presence of a powerful CYP2D6 inhibitor. The concentration-to-dose (C/D) ratio, where C includes R+9-OHR, is an index of total clearance from the body. A C/D ratio decreased by half is associated with CYP3A inducers or a lack of compliance, whereas an increased C/D ratio may indicate CYP2D6 PM phenotype, use of CYP2D6 and/or CYP3A4 inhibitors, or, possibly, renal insufficiency. In in-vitro studies, R and 9-OHR have similar receptor binding (except for blocking alpha(1)). 9-OHR may have less ability to enter the brain because of greater affinity for the transporter P-glycoprotein. The limited available paliperidone pharmacokinetic information suggests that there are four minor metabolic pathways. In contrast to R treatment, being a CYP2D6 PM may not be clinically relevant for paliperidone treatment. Information on paliperidone drug-drug interactions is limited. Renal excretion may be the major route of paliperidone elimination.
Clinicians can use R/9-OHR and the C/D ratios to interpret plasma R levels and guide treatment.
已有几种新型非典型抗精神病药物可供使用，但人们对它们的药理学知识可能并不广泛。
本综述旨在提高人们对利培酮（R）和帕利哌酮（9-羟基利培酮[9-OHR]）及其药代动力学和药效学的认识和了解。
作者对 R 和 9-OHR 的文献进行了回顾。
口服 R 的效力大约是口服 9-OHR 的两倍。接受 R 治疗的患者的 R 和 9-OHR 水平可能有助于临床医生开具 9-OHR 处方。在接受 R 治疗的患者中，R/9-OHR 浓度比是 CYP2D6 活性的指标；倒置比值（>1）表明 CYP2D6 弱代谢者（PM）或存在强效 CYP2D6 抑制剂。浓度与剂量（C/D）比值，其中 C 包括 R+9-OHR，是体内总清除率的指标。C/D 比值减半与 CYP3A 诱导剂或不遵守规定有关，而 C/D 比值增加可能表明 CYP2D6 PM 表型、CYP2D6 和/或 CYP3A4 抑制剂的使用，或者可能是肾功能不全。在体外研究中，R 和 9-OHR 具有相似的受体结合（除了阻断 alpha(1)）。由于对转运蛋白 P-糖蛋白的亲和力增加，9-OHR 可能进入大脑的能力较低。关于帕利哌酮药代动力学的有限信息表明存在四种次要代谢途径。与 R 治疗不同，作为 CYP2D6 PM 可能与帕利哌酮治疗无关。关于帕利哌酮药物相互作用的信息有限。肾排泄可能是帕利哌酮消除的主要途径。
临床医生可以使用 R/9-OHR 和 C/D 比值来解释血浆 R 水平并指导治疗。
