Population Pharmacokinetics and Exposure-Response of Albinterferon Alfa-2b
| Autor: | Timothy T. Bergsma, A. Corey, Daniel S. Stein, Matt N. Devalaraja, Haiying Sun, Matthew M. Riggs, G. Mani Subramanian, Jing Yu, James A. Rogers, Marc R. Gastonguay, Cecil Chen |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genotype Injections Subcutaneous Coefficient of variation Hepacivirus Antiviral Agents Models Biological Gastroenterology Young Adult chemistry.chemical_compound Albumins Internal medicine Ribavirin Statistics medicine Humans Tissue Distribution Pharmacology (medical) Adverse effect Aged Pharmacology Volume of distribution Dose-Response Relationship Drug business.industry Incidence (epidemiology) Interferon-alpha Hepatitis C Chronic Middle Aged Albinterferon Logistic Models chemistry Quartile Drug Therapy Combination Female business Albinterferon Alfa-2b medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 52:475-486 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270011399576 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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