OBJECTIVE The present study aimed to compare the pharmacokinetics of lamivudine in 300 mg once-daily and 150 mg twice-daily dosing regimens in HIV-infected Chinese patients. METHODS HIV-infected patients received lamivudine 300 mg once daily or 150 mg twice daily as part of a highly active antiretroviral therapy regimen. After the patients received lamivudine for at least 3 months, serial blood samples were collected for 24 hours. The samples were measured by a validated high-performance liquid chromatography (HPLC) assay. The pharmacokinetics of once-daily versus twice-daily dosing was evaluated by noncompartment models. RESULTS Ten patients received lamivudine 300 mg once daily and 5 patients received 150 mg twice daily. The C(max) was significantly higher in the once-daily arm than the twice-daily arm (2.23 vs 1.61 μg/mL, P <.05), whereas the C(min) was markedly lower (0.05 vs 0.12 μg/mL, P <.05). The half-lives were 3.32 hours and 2.62 hours, and AUC₂₄ values were 11.8 μg/mL·h and 13.0 μg/mL·h in the 300 mg once-daily and 150 mg twice-daily regimens, respectively (P >.05). CONCLUSIONS The shorter half-life was observed first in Chinese HIV patients with once- and twice-daily regimens. The 300 mg once-daily regimen was associated with lower trough concentrations and remarkable interpatient variability. Further studies in large groups of HIV patients are needed to confirm the influence of shorter half-lives in Chinese patients on efficacy and toxicity.