Effective use of modeling and simulation in designing bioequivalence and comparability studies of large-molecule compounds: the case of erythropoietin
| Autor: | Kumiko Miyata, Satofumi Iida, Takehiko Kawanishi, Kiyohiko Nakai |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Metabolic Clearance Rate Population Pharmacology Bioequivalence Models Biological Modeling and simulation Pharmacokinetics Japan Reticulocyte Count Statistics medicine Humans Pharmacology (medical) Computer Simulation education Erythropoietin education.field_of_study Cross-Over Studies business.industry Comparability Biosimilar Healthy Volunteers Molecular Weight Therapeutic Equivalency Research Design Pharmacodynamics Area Under Curve Hematinics Drug Monitoring business Software medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 53(6) |
| ISSN: | 0946-1965 |
| Popis: | OBJECTIVE Bioequivalence and comparability studies are necessary for changing formulations of large-molecule drugs, such as antibody drugs and protein products, and in the development of their biosimilars. This study is the first application of modeling and simulation (M&S) in the design of bioequivalence and comparability studies of erythropoietin as an example of a large-molecule drug. METHODS A novel population pharmacokinetic and pharmacodynamic (PPK/PD) model was developed for erythropoietin. Based on this PPK/PD model, the probabilities of success of bioequivalence and comparability studies were simulated with various numbers of subjects and samples. RESULTS The simulation indicated that the minimum numbers of subjects and samples required to satisfy the criteria for bioequivalence and comparability studies were as follows: fewest for the area under the serum concentration-time curve, more for the area under the efficacy-time curve, and most for the maximum serum concentration of erythropoietin. CONCLUSION These results suggested that M&S could be successfully applied in the design of bioequivalence and comparability studies of large-molecule drugs. |
| Databáze: | OpenAIRE |
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