{"title":"艾滋病、肝炎和其他抗病毒药物临床药理学国际研讨会摘要。","authors":"","doi":"10.1111/bcp.16309","DOIUrl":null,"url":null,"abstract":"<p><b>30</b></p><p><b>Population pharmacokinetics of ainuovirine and exposure–response analysis in the HIV-infected individuals</b></p><p>Su Bin<sup>1</sup>, Sun Jin<sup>1</sup>, Zhang Yihang<sup>1</sup>, Jiang Taiyi<sup>1</sup>, Xia Wei<sup>1</sup>, Zhang Tong<sup>1</sup>, Sun Lijun<sup>1</sup>, Wu Hao<sup>1</sup>, Qin Hong<sup>2</sup> and Yun Xinming<sup>2</sup></p><p><sup>1</sup><i>Beijing Youan Hospital, Capital Medical University;</i> <sup>2</sup><i>Jiangsu Aidea Pharmaceutical Co., Ltd</i></p><p><b>Objective:</b> Ainuovirine (ANV) is a novel new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of human immunodeficiency virus type 1 (HIV-1) infection. This study aimed to evaluate the population pharmacokinetic profile and exposure-response relationship of ANV among people living with HIV (PLWH).</p><p><b>Methods:</b> Plasma concentration–time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the population pharmacokinetic (PopPK) model. Exposure estimates obtained from the final model were used in exposure–response analysis for virologic and safety responses.</p><p><b>Results:</b> ANV exhibited a non-linear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (RSE%) for CL/F was 6.46 L/h (15.0), 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><p><b>Conclusions:</b> Our PopPK model supported ANV 150 mg once daily as the recommended dose for PLWH, 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.</p><p><b>Keywords:</b> ainuovirine, expose–response model, HIV, population pharmacokinetics</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"90 S1","pages":"21"},"PeriodicalIF":3.1000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16309","citationCount":"0","resultStr":"{\"title\":\"Population pharmacokinetics of ainuovirine and exposure–response analysis in the HIV-infected individuals\",\"authors\":\"\",\"doi\":\"10.1111/bcp.16309\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>30</b></p><p><b>Population pharmacokinetics of ainuovirine and exposure–response analysis in the HIV-infected individuals</b></p><p>Su Bin<sup>1</sup>, Sun Jin<sup>1</sup>, Zhang Yihang<sup>1</sup>, Jiang Taiyi<sup>1</sup>, Xia Wei<sup>1</sup>, Zhang Tong<sup>1</sup>, Sun Lijun<sup>1</sup>, Wu Hao<sup>1</sup>, Qin Hong<sup>2</sup> and Yun Xinming<sup>2</sup></p><p><sup>1</sup><i>Beijing Youan Hospital, Capital Medical University;</i> <sup>2</sup><i>Jiangsu Aidea Pharmaceutical Co., Ltd</i></p><p><b>Objective:</b> Ainuovirine (ANV) is a novel new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of human immunodeficiency virus type 1 (HIV-1) infection. This study aimed to evaluate the population pharmacokinetic profile and exposure-response relationship of ANV among people living with HIV (PLWH).</p><p><b>Methods:</b> Plasma concentration–time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the population pharmacokinetic (PopPK) model. Exposure estimates obtained from the final model were used in exposure–response analysis for virologic and safety responses.</p><p><b>Results:</b> ANV exhibited a non-linear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (RSE%) for CL/F was 6.46 L/h (15.0), 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><p><b>Conclusions:</b> Our PopPK model supported ANV 150 mg once daily as the recommended dose for PLWH, requiring no dose adjustment for the studied factors. 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引用次数: 0
摘要
30阿奴韦林在HIV感染者中的群体药代动力学及暴露-反应分析苏斌1, 孙进1, 张一航1, 蒋太一1, 夏伟1, 张彤1, 孙立军1, 吴昊1, 秦红2, 云新明21首都医科大学附属北京佑安医院；2江苏爱迪药业股份有限公司目的：阿奴韦林（ANV）是一种新型的新一代非核苷类逆转录酶抑制剂（NNRTI），用于治疗人类免疫缺陷病毒1型（HIV-1）感染：Ainuovirine（ANV）是一种新型的新一代非核苷类逆转录酶抑制剂（NNRTI），用于治疗人类免疫缺陷病毒1型（HIV-1）感染。本研究旨在评估 ANV 在 HIV 感染者（PLWH）中的群体药代动力学特征和暴露-反应关系：方法：汇集 ANV 1 期和 3 期临床试验的血浆浓度-时间数据，建立群体药代动力学（PopPK）模型。从最终模型中得到的暴露估计值被用于病毒学和安全性反应的暴露-反应分析：结果：ANV表现出非线性药代动力学特征，用一阶消除的两室模型对其进行了最佳描述。没有明显的协变量与 ANV 的药代动力学参数相关。CL/F的PopPK参数估计值（RSE%）为6.46升/小时（15.0），多次给药后ANV的清除率增加。暴露-反应模型显示，48周时的病毒学反应（HIV-RNA <50拷贝/毫升）与暴露量无显著相关性，但不良事件的发生率随着暴露量的增加而增加：我们的 PopPK 模型支持将 ANV 150 毫克、每日一次作为 PLWH 的推荐剂量，无需根据研究因素调整剂量。由于不良反应有随着暴露量增加而增加的趋势，因此在临床实践中可能需要优化ANV的剂量。
Population pharmacokinetics of ainuovirine and exposure–response analysis in the HIV-infected individuals
30
Population pharmacokinetics of ainuovirine and exposure–response analysis in the HIV-infected individuals
Su Bin1, Sun Jin1, Zhang Yihang1, Jiang Taiyi1, Xia Wei1, Zhang Tong1, Sun Lijun1, Wu Hao1, Qin Hong2 and Yun Xinming2
1Beijing Youan Hospital, Capital Medical University;2Jiangsu Aidea Pharmaceutical Co., Ltd
Objective: Ainuovirine (ANV) is a novel new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of human immunodeficiency virus type 1 (HIV-1) infection. This study aimed to evaluate the population pharmacokinetic profile and exposure-response relationship of ANV among people living with HIV (PLWH).
Methods: Plasma concentration–time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the population pharmacokinetic (PopPK) model. Exposure estimates obtained from the final model were used in exposure–response analysis for virologic and safety responses.
Results: ANV exhibited a non-linear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (RSE%) for CL/F was 6.46 L/h (15.0), 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.
Conclusions: Our PopPK model supported ANV 150 mg once daily as the recommended dose for PLWH, 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.
Keywords: ainuovirine, expose–response model, HIV, population pharmacokinetics
期刊介绍：
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.
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