Do Chinese HIV-infected adult patients with altered renal function need to adjust tenofovir disoproxil fumarate dosage? A population pharmacokinetics analysis

• Published in: European journal of pharmaceutical sciences 2024-10, Vol.201, p.106851, Article 106851
• Main Authors: Chen, Rui, Zhang, Ren-fang, Xing, Ya-ru, Wang, Jiang-rong, Liu, Li, Yin, Lin, Li, Ying-ying, Jiao, Zheng, Zhang, Li-jun
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; China; East Asian People; Female; Glomerular Filtration Rate; HIV; HIV Infections - drug therapy; Humans; Male; Middle Aged; Models, Biological; Monte Carlo Method; Monte Carlo simulation; Population pharmacokinetics; Renal impairment; Tenofovir; Tenofovir - administration & dosage; Tenofovir - pharmacokinetics; Young Adult
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2024.106851

Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir (TFV), is an effective drug in treating patients infected with human immunodeficiency virus (HIV). Previous population pharmacokinetics (PPK) studies have showed the large variabilities in PK of TFV. Furthermore, limited information was known in Chinese populations. Therefore, the aim of this study was to characterize PPK of TDF in Chinese and identify factors that may affect its PK. TFV concentrations (n = 552) from 30 healthy subjects and 162 HIV-infected Chinese adult patients were pooled for PPK analysis by a nonlinear mixed-effects method. The PK of TFV was adequately described as a two-compartment model with first order absorption and elimination. The typical apparent clearance (CL/F) of TFV in 70-kg adults was 137 L/h, higher than that reported in Caucasians and Blacks (45.8–93 L/h). Estimated glomerular filtration rate was identified to be a significant factor influencing CL/F. Monte Carlo simulation showed that the exposure of standard dosing regimen of TDF 300 mg every 24 h in Chinese people with mild renal impairment (60 to 90 ml/min/1.73 m2) was close to that in individuals with normal renal function (90 mL/min). Dose adjustment is not required for patients with mild renal impairment. Our study might offer new clues for optimal dosing strategies in Chinese patients with HIV-infected. [Display omitted]