Population pharmacokinetics of Ainuovirine and exposure-response analysis in human immunodeficiency virus-infected individuals

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外文摘要：Background:Ainuovirine(ANV)is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus(HIV)type 1 infection.This study aimed to evaluate the population pharmacokinetic(PopPK)profile and exposure-response relationship of ANV among people living with HIV.Methods:Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model.Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results:ANV exhibited a nonlinear pharmacokinetic profile,which was best described by a two-compartment model with first-or-der elimination.There were no significant covariates correlated to the pharmacokinetic parameters of ANV.The PopPK parameter estimate(relative standard error[％])for clearance adjusted for bioavailability(CL/F)was 6.46(15.00)L/h,and the clearance of ANV increased after multiple doses.The exposure-response model revealed no significant correlation between the virologic response(HIV-RNA＜50 copies/mL)at 48 weeks and the exposure,but the incidence of adverse events increased with the increasing exposure(P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141,respectively).Conclusions:Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV,requiring no dose adjustment for the studied factors.Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.

外文关键词：

Human immunodeficiency virusAinuovirinePopulation pharmacokineticsExpose-response modelSafetyAcquired immune deficiency syndromeAntiretroviral therapy

作者：

Xiaoxu Han、Jin Sun、Yihang Zhang、Taiyi Jiang、Qingshan Zheng、Haiyan Peng、Yao Wang、Wei Xia、Tong Zhang、Lijun Sun、Xinming Yun、Hong Qin、Hao Wu、Bin Su

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作者单位：

Beijing Key Laboratory for HIV/AIDS Research,Clinical and Research Center for Infectious Diseases,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China

Beijing BioVoice Technology Co.,Ltd.,Beijing 100068,China

Beijing CO-CRO Medical Development Co.,Ltd.,Beijing 100061,China

Jiangsu Aidea Pharmaceutical Co.,Ltd.,Nanjing,Jiangsu 211899,China

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基金：

National"Thirteenth Fiveyear Period"Major Innovative Drug Research and Development Key Project of the Ministry of Science anHigh-Level Public Health Specialized Talents Project of Beijing Municipal Health CommissionHigh-Level Public Health Specialized Talents Project of Beijing Municipal Health Commissionthe"Climbing the peak(Dengfeng)"Talent Training Program of Beijing Hospitals AuthorityBeijing Health Technologies Promotion ProgramBeijing Key Laboratory for HIV/AIDS Research

项目编号：

2017ZX092010072022-1-0072022-2-018DFL20191701BHTPP202002BZ0089

出版年：

2024

DOI：

10.1097/CM9.0000000000002917

中华医学杂志(英文版)

中华医学会

中华医学杂志(英文版)

CSTPCD

影响因子：0.838

ISSN：0366-6999

年,卷(期)：2024.137(20)