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- Title
Population Pharmacokinetics and Exposure-Response of Albinterferon Alfa-2b.
- Authors
Riggs, Matthew M.; Bergsma, Timothy T.; Rogers, James A.; Gastonguay, Marc R.; Subramanian, G. Mani; Chen, Cecil; Devalaraja, Matt; Corey, Alfred E.; Sun, Haiying; Yu, Jing; Stein, Daniel S.
- Abstract
Albinterferon alfa-2b (albIFN) has been studied for treatment of chronic hepatitis C virus (HCV). A population pharmacokinetics model was developed using nonlinear mixed-effects modeling. Efficacy/safety exposure-response relationships were assessed for subcutaneous albIFN doses (900–1800 µg once every 2 or 4 weeks) administered for either 24 weeks (HCV genotypes 2/3) or 48 weeks (genotype 1), plus daily oral ribavirin. Sustained virologic response (SVR) exposure-response was modeled using logistic regression. Adverse event incidence was tabulated versus exposure quartiles. First-order absorption rate constant (0.0148 h−1), apparent clearance (38.9 mL/h), and apparent volume of distribution (11.6 L) had interindividual variances (coefficient of variation) of 21%, 34%, and 24%, respectively. Residual variance estimates were 27% (coefficient of variation) and 1.51 ng/mL (standard deviation). For the only explanatory covariate—body weight—exposure decreased as weight increased. Important SVR predictors included baseline HCV RNA, fibrosis score, and black race (genotype 1); SVR was minimally related to exposure. Most adverse events had similar incidence rates across exposure quartiles. Some adverse events had a higher incidence in the upper exposure quartile without evidence of exposure-response across the lower quartiles. Given the lack of consistent efficacy/safety exposure-response relationships, further investigation is necessary to optimize albIFN dosing.
- Subjects
ASIANS; BIOTRANSFORMATION (Metabolism); BLACK people; CONFIDENCE intervals; ENZYME-linked immunosorbent assay; HEPATITIS C; INTERFERONS; RACE; STATISTICAL sampling; WHITE people; ALBUMINS; RANDOMIZED controlled trials; DATA analysis software; DESCRIPTIVE statistics
- Publication
Journal of Clinical Pharmacology, 2012, Vol 52, Issue 4, p475
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1177/0091270011399576