Suppr超能文献

使用来自CATIE研究的高度稀疏采样测量数据进行利培酮的群体药代动力学分析。

Population pharmacokinetic analysis for risperidone using highly sparse sampling measurements from the CATIE study.

作者信息

Feng Yan, Pollock Bruce G, Coley Kim, Marder Stephen, Miller Del, Kirshner Margaret, Aravagiri Manickam, Schneider Lon, Bies Robert R

机构信息

Strategic Modeling and Simulation Group, Bristol-Myers Squibb Co., Princeton, NJ, USA.

出版信息

Br J Clin Pharmacol. 2008 Nov;66(5):629-39. doi: 10.1111/j.1365-2125.2008.03276.x. Epub 2008 Jul 31.

Abstract

AIMS

To characterize pharmacokinetic (PK) variability of risperidone and 9-OH risperidone using sparse sampling and to evaluate the effect of covariates on PK parameters.

METHODS

PK analysis used plasma samples collected from the Clinical Antipsychotic Trials of Intervention Effectiveness. A nonlinear mixed-effects model was developed using NONMEM to describe simultaneously the risperidone and 9-OH risperidone concentration-time profile. Covariate effects on risperidone and 9-OH risperidone PK parameters were assessed, including age, weight, sex, smoking status, race and concomitant medications.

RESULTS

PK samples comprised 1236 risperidone and 1236 9-OH risperidone concentrations from 490 subjects that were available for analysis. Ages ranged from 18 to 93 years. Population PK submodels for both risperidone and 9-OH risperidone with first-order absorption were selected to describe the concentration-time profile of risperidone and 9-OH risperidone. A mixture model was incorporated with risperidone clearance (CL) separately estimated for three subpopulations [poor metabolizer (PM), extensive metabolizer (EM) and intermediate metabolizer (IM)]. Age significantly affected 9-OH risperidone clearance. Population parameter estimates for CL in PM, IM and EM were 12.9, 36 and 65.4 l h(-1) and parameter estimates for risperidone half-life in PM, IM and EM were 25, 8.5 and 4.7 h, respectively.

CONCLUSIONS

A one-compartment mixture model with first-order absorption adequately described the risperidone and 9-OH risperidone concentrations. Age was identified as a significant covariate on 9-OH risperidone clearance in this study.

摘要

目的

采用稀疏采样法描述利培酮和9-羟基利培酮的药代动力学(PK)变异性,并评估协变量对PK参数的影响。

方法

PK分析使用从临床抗精神病药物干预有效性试验中收集的血浆样本。使用NONMEM开发非线性混合效应模型,以同时描述利培酮和9-羟基利培酮的浓度-时间曲线。评估协变量对利培酮和9-羟基利培酮PK参数的影响,包括年龄、体重、性别、吸烟状况、种族和合并用药情况。

结果

PK样本包括来自490名受试者的1236个利培酮浓度和1236个9-羟基利培酮浓度,可用于分析。年龄范围为18至93岁。选择具有一级吸收的利培酮和9-羟基利培酮的群体PK子模型来描述利培酮和9-羟基利培酮的浓度-时间曲线。采用混合模型,分别对三个亚组[慢代谢者(PM)、快代谢者(EM)和中间代谢者(IM)]单独估计利培酮清除率(CL)。年龄显著影响9-羟基利培酮的清除率。PM、IM和EM中CL的群体参数估计值分别为12.9、36和65.4 l h⁻¹,PM、IM和EM中利培酮半衰期的参数估计值分别为25、8.5和4.7 h。

结论

具有一级吸收的单室混合模型能充分描述利培酮和9-羟基利培酮的浓度。在本研究中,年龄被确定为9-羟基利培酮清除率的显著协变量。

相似文献

1
Population pharmacokinetic analysis for risperidone using highly sparse sampling measurements from the CATIE study.
Br J Clin Pharmacol. 2008 Nov;66(5):629-39. doi: 10.1111/j.1365-2125.2008.03276.x. Epub 2008 Jul 31.
3
Population pharmacokinetics of risperidone and 9-hydroxyrisperidone in patients with acute episodes associated with bipolar I disorder.
J Pharmacokinet Pharmacodyn. 2007 Apr;34(2):183-206. doi: 10.1007/s10928-006-9040-2. Epub 2006 Nov 29.
9
Development of a population pharmacokinetic model for the novel long-acting injectable antipsychotic risperidone ISM®.
Br J Clin Pharmacol. 2024 Sep;90(9):2256-2270. doi: 10.1111/bcp.16115. Epub 2024 Jun 12.

引用本文的文献

1
Population Pharmacokinetics of Risperidone and Paliperidone in Schizophrenia: A Systematic Review.
Pharmaceuticals (Basel). 2025 May 8;18(5):698. doi: 10.3390/ph18050698.
2
Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo.
Eur J Clin Pharmacol. 2024 Oct;80(10):1531-1541. doi: 10.1007/s00228-024-03721-6. Epub 2024 Jul 4.
4
External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data.
Front Pharmacol. 2022 Mar 17;13:817276. doi: 10.3389/fphar.2022.817276. eCollection 2022.
6
Evaluation of the estimation and classification performance of NONMEM when applying mixture model for drug clearance.
CPT Pharmacometrics Syst Pharmacol. 2021 Dec;10(12):1564-1577. doi: 10.1002/psp4.12726. Epub 2021 Oct 24.
7
Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics.
Pharmaceutics. 2021 Jun 23;13(7):935. doi: 10.3390/pharmaceutics13070935.
9
Linking Tumor Growth Dynamics to Survival in Ipilimumab-Treated Patients With Advanced Melanoma Using Mixture Tumor Growth Dynamic Modeling.
CPT Pharmacometrics Syst Pharmacol. 2019 Nov;8(11):825-834. doi: 10.1002/psp4.12454. Epub 2019 Aug 13.
10
Population Pharmacokinetic Modelling of Pyrazinamide and Pyrazinoic Acid in Patients with Multi-Drug Resistant Tuberculosis.
Eur J Drug Metab Pharmacokinet. 2019 Aug;44(4):519-530. doi: 10.1007/s13318-018-00540-w.

本文引用的文献

1
Population pharmacokinetics of risperidone and 9-hydroxyrisperidone in patients with acute episodes associated with bipolar I disorder.
J Pharmacokinet Pharmacodyn. 2007 Apr;34(2):183-206. doi: 10.1007/s10928-006-9040-2. Epub 2006 Nov 29.
2
Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.
N Engl J Med. 2006 Oct 12;355(15):1525-38. doi: 10.1056/NEJMoa061240.
3
Paroxetine: population pharmacokinetic analysis in late-life depression using sparse concentration sampling.
Br J Clin Pharmacol. 2006 May;61(5):558-69. doi: 10.1111/j.1365-2125.2006.02629.x.
4
Population pharmacokinetic analysis of drug-drug interactions among risperidone, bupropion, and sertraline in CF1 mice.
Psychopharmacology (Berl). 2006 Jan;183(4):490-9. doi: 10.1007/s00213-005-0209-y. Epub 2005 Nov 9.
5
Dose-dependent interaction of paroxetine with risperidone in schizophrenic patients.
J Clin Psychopharmacol. 2005 Dec;25(6):527-32. doi: 10.1097/01.jcp.0000185428.02430.c7.
7
Influence of age and gender on risperidone plasma concentrations.
J Psychopharmacol. 2005 Jul;19(4):395-401. doi: 10.1177/0269881105053306.
9
Utility of sparse concentration sampling for citalopram in elderly clinical trial subjects.
J Clin Pharmacol. 2004 Dec;44(12):1352-9. doi: 10.1177/0091270004269647.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验