Population pharmacokinetics of ainuovirine and exposure–response analysis in the HIV-infected individuals

Abstract

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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