title: Pharmacokinetics of telbivudine in subjects with various degrees of hepatic impairment.
abstract: 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.
authors.affiliation: Idenix Pharmaceuticals Inc., 60 Hampshire Street, Cambridge, MA 02139, USA. zhou.xiao-jian@idenix.com
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.forename: Harry W
authors.initials: HW
authors.lastname: Alcorn
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.forename: Gloria
authors.initials: G
authors.lastname: Dubuc Patrick
authors.forename: George C
authors.initials: GC
authors.lastname: Chao
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Brown
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D011744:Pyrimidinones; D000077712:Telbivudine; D013936:Thymidine