Study of in silico bioequivalence of drugs with long half-life for evaluation of sampling schedule of biological samples

• Grant number: 10/05706-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2012
• End date: July 31, 2014
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Eunice Kazue Kano
• Grantee: Eunice Kazue Kano
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In recent years, there has been a significant growth in published scientific papers that use in silico simulations, based on complex phenomena observed in in vivo studies to analyze pharmacokinetic and pharmacodynamic properties of a medicine, and in bioequivalence studies. Bioequivalence can be defined as an in vivo evaluation of the rate and extension of absorption of a drug from its pharmaceutical form and becomes available in the action site. For drugs with long elimination half-life, bioequivalence studies involve great number of samples and take months. The evaluation of the possibility of reducing the number of samples per assay is important because ethical and financial aspects are involved. Due to this reason, the objective of this project is to evaluate the influence of sampling schedule in the final result of bioequivalence studies considering drugs with long half-life using mathematical simulations. The results of simulations will be compared with a real in vivo study. The simulations of bioequivalence studies will be performed using two models: based on minimum and maximum values of pharmacokinetic parameters and based on intra and inter subject variability. Differences sampling schedules and different doses of fluconazole will be used to simulate difference in bioavailability. The results of simulations will be used to plan the in vivo study. This study will be conducted in healthy volunteers, and they will receive two doses of fluconazole. This investigation will bring benefits for subjects involved, wich will have reduced exposure to risks, as well as for biofarmacy researchers with the reduction of costs associated with the assays. (AU)