Pharmacokinetics of telbivudine in subjects with various degrees of hepatic impairment.
This study evaluated the effect of hepatic impairment on the pharmacokinetics of telbivudine, an investigational nucleoside antiviral for the treatment of chronic hepatitis B virus infection. Twenty-four subjects were assigned to four hepatic function groups (normal function and mild, moderate, and severe impairment, with six subjects in each group) on the basis of Child-Pugh scores. The subjects were administered a single oral dose of 600 mg telbivudine, and blood samples were collected over a 48-h interval for pharmacokinetic analyses. Telbivudine was well tolerated by all subjects. Telbivudine plasma concentration-time profiles were similar across the four hepatic function groups. The principal pharmacokinetic parameters of drug exposure, i.e., the maximum plasma concentration and area under the drug concentration-time curve, were comparable between subjects with various degrees of hepatic impairment and those with normal hepatic function. Results from this single-dose pharmacokinetic assessment therefore provide a pharmacologic rationale for further evaluation of the safety and efficacy of telbivudine in hepatitis B virus-infected patients with decompensated liver diseases.
Zhou
Xiao-Jian
XJ
Idenix Pharmaceuticals Inc., 60 Hampshire Street, Cambridge, MA 02139, USA. zhou.xiao-jian@idenix.com
Marbury
Thomas C
TC
Alcorn
Harry W
HW
Smith
William B
WB
Dubuc Patrick
Gloria
G
Chao
George C
GC
Brown
Nathaniel A
NA
D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009705:Nucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012720:Severity of Illness Index; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D013936:Thymidine