Abstract: Objective To investigate strategies for efficacy evaluation of oral dosage forms of pro-drugs based on the findings related to oral dosage forms of clindamycin palmitate hydrochloride. Methods Beagles were used to determine the drug concentration in blood. A physiologically based pharmacokinetic (PBPK) model was established and validated with the data collected from animal experiments. The efficacy was compared between clindamycin palmitate hydrochloride dispersible tablets and suspension using inter-species extrapolation and population analog approaches. Results The results showed that the peak time of blood concentration (t_max) was 1.9 hours for both the testing sample and reference sample. The maximum concentration (c_max) was 1.215 and 1.150 μg/mL, respectively, and the 90% confidence interval of the ratio between average values was 95.6%~115.8%.The average value of the area under the curve (AUC_0-t) was 5.462 and 5.331 μg·h/mL respectively,and the 90% confidence interval of the ratio between average values was 88.5%~116.4%. The testing sample and reference sample had similar pharmacodynamics parameters and it was predicted that testing sample was bioequivalent to the reference sample based on analysis of t_max, c_max and AUC_0-t parameters. There was no significant difference between the testing and reference samples, for the gram-positive bacterium the antimicrobial inhibition time was 11.7 and 11.6 hours respectively, compared to 9.9 and 9.7 hours for the gram-negative bacterium. Conclusion The strategy developed in this research, which used data from only a few animal experiments, has considerable advantages over the in-vitro evaluating methods in terms of accuracy and reliability. It can be used as a low-cost and reliable pre-evaluation tool before conducting the conventional BE study.

Key words: clindamycin palmitate hydrochloride, efficacy evaluation, PBPK model, population analog