title: Pooled model-based approach to compare the pharmacokinetics of entecavir between Japanese and non-Japanese chronic hepatitis B patients.
abstract: This study evaluated the population pharmacokinetics (PK) of entecavir in Japanese patients with chronic hepatitis B infection enrolled in 2 Japanese phase IIb clinical trials and compared them to non-Japanese patients enrolled in global phase II trials. The objectives were to identify significant and clinically meaningful covariate effects on entecavir population pharmacokinetic parameters and assess whether differences exist between Japanese and non-Japanese patients. A total of 843 observations were obtained from 142 patients who received once daily administration of entecavir at 0.1, 0.5, and 1.0 mg doses in the 2 Japanese studies. Consistent with findings in non-Japanese patients, creatinine clearance estimated with ideal body weight (ICrCL) was found to be statistically significant for clearance in a 2-compartment model. Also, the entecavir dose was identified as a covariate on intercompartmental clearance. Age, gender, and hepatic function were not identified as covariate for clearance. The estimated population average of oral clearance in a typical patient with a reference ICrCL value of 100 mL/min was 26.4 L/h (interindividual variability: 19.4%). This model-based analysis indicates that the PK of entecavir are similar in Japanese and non-Japanese chronic hepatitis B patients.
authors.affiliation: Research and Development Japan, Bristol-Myers K.K., Shinjuku i-Land Tower, 6-5-1 Nishi-Shinjuku, Tokyo 163-1328, Japan. hiroyuki.yoshitsugu@bms.com
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshitsugu
authors.forename: Takao
authors.initials: T
authors.lastname: Sakurai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Amit
authors.initials: A
authors.lastname: Roy
authors.forename: Marc
authors.initials: M
authors.lastname: Bifano
authors.forename: Marc
authors.initials: M
authors.lastname: Pfister
authors.forename: Taku
authors.initials: T
authors.lastname: Seriu
authors.forename: Masaki
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D044466:Asian People; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015233:Models, Statistical
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine; D003404:Creatinine