Single-dose and multiple-dose pharmacokinetics and safety of telbivudine after oral administration in healthy Chinese subjects.
The pharmacokinetics of telbivudine, an L-nucleoside with potent activity against hepatitis B virus, was assessed in 42 healthy Chinese volunteers. Subjects were assigned to receive a single oral dose of 200, 400, or 800 mg telbivudine or repeat doses of 600 mg/d. Telbivudine was absorbed rapidly and exhibited dose-related plasma exposure. After reaching maximum concentration (C(max)) at a median time of 2.0 to 2.5 hours, plasma disposition of the drug was biphasic with a mean terminal half-life ranging from 39.4 to 49.1 hours. Telbivudine accumulated slightly after repeat doses, and steady state was reached after 5 to 6 consecutive doses of 600 mg/d. The mean steady-state C(max) and area under the plasma concentration-time curve over the dosing interval of telbivudine 600 mg were 3.7 microg/mL and 26.1 microg x h/mL, respectively. Cumulative urinary excretion of telbivudine over 32 hours represented 24.4% of the administered dose, with a mean renal clearance of 6.6 L/h. Telbivudine was well tolerated in the studied dose range in healthy Chinese subjects, with no pattern of dose-related clinical or laboratory adverse events.
Hu
Pei
P
Peking Union Medical College Hospital, Beijing, People's Republic of China.
Jiang
Ji
J
Wang
Hongyun
H
Pietropaolo
Keith
K
Chao
George C
GC
Brown
Nathaniel A
NA
Zhou
Xiao-Jian
XJ
D000284:Administration, Oral; D000328:Adult; D002681:China; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006262:Health; D006801:Humans; D008297:Male; D009705:Nucleosides / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives
D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D013936:Thymidine