A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials

摘要: AIMS The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due between formulations or intrasubject pharmacokinetic variability active substance. Methods The designed as a retrospective reanalysis existing studies. Nine replicate design bioequivalence studies representing six classes – i.e. for alendronate, atorvastatin, cyclosporin, ebastine, exemestane, mycophenolate mofetil, ropinirole were retrieved from Dutch Medicines Regulatory Authority. Results In most studies, comparable brand-name [in range 0.01–0.24 area under concentration–time curve (AUCt) 0.02–0.29 plasma concentration (Cmax) on log scale] (0.01–0.23 AUCt 0.08–0.33 Cmax) drugs, with switching those drugs 0.06–0.33 Cmax). The variance related subject-by-formulation interaction could be considered negligible (–0.069 0.047 –0.091 0.02 Cmax). Conclusion In investigated variation seen when patient is switched that following repeated administration patient. Only seems play crucial decisive role seen; no additional formulation-dependent observed switching. Thus, our data support that, medicines included investigation, clinical pharmacological perspective, benefit–risk balance drug.