Steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected Chinese patients

Abstract

Background: The pharmacokinetic (PK) profile of tenofovir disoproxil fumarate in Chinese adults infected with HIV is unknown.

Methods: A pilot, prospective, open-label study was performed to investigate the steady-state PK profile of tenofovir disoproxil fumarate in 15 Chinese HIV-infected patients among whom eight patients were treated with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400/100 mg lopinavir/ritonavir, and seven with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400 mg nevirapine. The plasma concentrations of tenofovir over the 24-h dosing interval were determined by HPLC. The PK parameters were calculated using the non-compartmental model in WinNonlin software.

Results: The PK parameters of tenofovir in the 15 patients were determined as follows (mean ± SD): AUC_{(0-24 h)}, 4074.7 ± 1551.9 ng•h/mL; C_max,ss, 447.1 ± 217.4 ng/mL; C_trough,ss, 98.7 ± 36.7 ng/mL; t_max,ss, 1.3 ± 0.4 h; plasma t_1/2, 21.8 ± 7.6 h; and CL_ss/F, 45.8 ± 13.0 L/h.

Conclusion: Tenofovir demonstrated slower elimination rate and increased plasma concentration in Chinese patients compared to previously published data from Caucasian or African subjects, which may be associated with the higher incidences of renal and bone resorption dysfunction observed in our patient population. Clinicians should be cautious of the differing PK characteristics of tenofovir among people of different races.

Keywords: Chinese; HIV/AIDS; lopinavir/ritonavir; pharmacokinetics; tenofovir disoproxil fumarate.