Steady-state pharmacokinetics of lamivudine once-daily versus twice-daily dosing in Chinese HIV-infected patients.
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.
Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences-Peking Union Medical College, Beijing, China.
Min
M
Ye
Lu
L
Wang
Qiang
Q
Fu
Zhu
Z
Zhu
Peng
P
Li
Taisheng
T
Li
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D019540:Area Under Curve; D002681:China; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development*; D006207:Half-Life; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine