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.
Population Pharmacokinetics and Exposure‐Response of Albinterferon Alfa‐2b
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Media type:
E-Article
Title:
Population Pharmacokinetics and Exposure‐Response of Albinterferon Alfa‐2b
Contributor:
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.
Published:
Wiley, 2012
Published in:
The Journal of Clinical Pharmacology, 52 (2012) 4, Seite 475-486
Description:
<jats:p>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<jats:sup>−1</jats:sup>), 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.</jats:p>