OBJECTIVETo evaluate the pharmacokinetic profile of telbivudine in healthy Chinese subjects after oral administration of single and multiple doses.

METHODSForty-two healthy adult male and female subjects 18-40 years of age were randomized into four telbivudine dosing groups of 200 mg, 400 mg, 600 mg and 800 mg. Subjects in the 600 mg group received both a single dose and once daily multiple doses for 8 consecutive days. Telbivudine concentrations in plasma and urine samples collected at different time points before and after the drug administration were measured using HPLC-MS/MS. Pharmacokinetic parameters were calculated by using the non-compartmental approach.

RESULTSAfter a single dose of 200 mg, 400 mg, 600 mg and 800 mg, tmax (median) were 2.50, 2.00, 2.00 and 2.50 hours respectively; t1/2 were (43.3 +/- 15.2) h, (49.1 +/- 14.4) h, (39.4 +/- 12.1) h and (46.7 +/- 20.8) h respectively; Cmax were (1,753.2 +/- 389.0) ng/ml, (2,586.7 +/- 871.4) ng/ml, (3,703.6 +/- 1,219.0) ng/ml and (3454.6 +/- 953.9) ng/ml respectively; AUC(0-infinity) were (12,843.2 +/- 2,925.6) ng.h(-1).ml(-1), (22,948.9 +/- 5,721.0) ng.h(-1)/ml(-1), (26,440.5 +/- 8,938.1) ng.h(-1).ml(-1) and (28, 820.9 +/- 7 912.9) ng.h(-1).ml(-1) respectively, and CL(R) (600 mg) was (6,545.6 +/- 1 504.4) ml/h. The AUCss from multiple doses was (1,088.5 +/- 299.8) ng/ml; Cmax and AUC accumulation ratio were 1.02 +/- 0.21 and 1.23 +/- 0.26 respectively, which implicated moderated accumulation.

CONCLUSIONPharmacokinetic parameters of telbivudine in Chinese healthy subjects were determined.

Adolescent ; Adult ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Nucleosides ; pharmacokinetics ; Pyrimidinones ; pharmacokinetics ; Thymidine ; analogs & derivatives ; Young Adult