Effect of Different Sampling Schedules on Results of Bioavailability and Bioequivalence Studies: Evaluation by Means of Monte Carlo Simulations

Abstract

Bioavailability and bioequivalence study is one of the most frequently performed investigations in clinical trials. Bioequivalence testing is based on the assumption that 2 drug products will be therapeutically equivalent when they are equivalent in the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed and becomes available at the site of drug action. In recent years there has been a significant growth in published papers that use studies based on mathematical simulations to analyze pharmacokinetic and pharmacodynamic properties of drugs, including bioavailability and bioequivalence aspects. The goal of this study is to evaluate the usefulness of studies as a tool in the planning of bioequivalence, bioavailability and other pharmacokinetic assays, e.g., to determine an appropriate sampling schedule. Monte Carlo simulations were used to define adequate blood sampling schedules for a bioequivalence assay comparing 2 different formulations of cefadroxil oral suspensions. bioequivalence studies comparing different formulation of cefadroxil oral suspensions using various sampling schedules were performed using models. An in vivo study was conducted to confirm results. The results of and in vivo bioequivalence studies demonstrated that schedules with fewer sampling times are as efficient as schedules with larger numbers of sampling times in the assessment of bioequivalence, but only if T is included as a sampling time. It was also concluded that studies are useful tools in the planning of bioequivalence, bioavailability and other pharmacokinetic in vivo assays.

Computational design of clinical trials using a combination of simulation and the genetic algorithm

“…be included at the time of blood sampling 26 -the number of options may decrease considerably. However, numerous options remain.…”

“… 40 , 41 In this first case, there were ~10 13 combinations of seven to eight points selected from 49 timepoint candidates. Considering the feasibility of the study, and the standard theory of a sampling schedule—for example, T max must be included at the time of blood sampling 26 —the number of options may decrease considerably. However, numerous options remain.…”

“…Because the frequency and sample volume of blood collection are more limited in pediatrics than in adults, the blood sampling schedule must be refined. Current schedule optimization methods are unable to reduce the sampling to a satisfactory level 25,26 . Hence, a novel approach for minimizing blood drawing timepoints is required.…”

“…Current schedule optimization methods are unable to reduce the sampling to a satisfactory level. 25 , 26 Hence, a novel approach for minimizing blood drawing timepoints is required.…”

Bioequivalence and Safety Assessment of Two Formulations of Metformin Hydrochloride Sustained-Release Tablets (Yuantang® SR and Glucophage® XR) Under Fed Conditions in Healthy Chinese Adult Subjects: An Open-Label, Two-Way Crossover, Sequence Randomized Phase I Clinical Trial

“…The most important objective of a bioequivalence trial is to ensure that the two formulations have similar rates and extents of absorption, which would indicate that they are therapeutically equivalent [ 27 , 28 ]. After a single drug dose, particularly for fast-release formulations, C max reflects the absorption rate and AUC reflects the degree of absorption; these represent the primary pharmacokinetic parameters.…”