A Comparative Study of PBPK Model and Allometric Growth Model of Azithromycin in Extrapolation of Adult Pharmacokinetic Data to Pediatric Population / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish an adult-pediatric transformation model of azithromycin to provide guiding recommendations for clinical using of pediatrics, reduce the risk of medicationfor children, and achieve clinical personalized medication for children. METHODS: The relevant literature was reviewed. The physiological parameters of the azithromycin oral administration test in adults combined with the drug-specific parameters of azithromycin were used to establish an allometric growth model, PBPK model. According to the clinical data of oral azithromycin extracted from individual children, the correctness of the parameter scaling formulas of these two models was verified. These two models were further used to simulate the pharmacokinetic parameters of children and calculate the relative deviation and relative standard error of these parameters. RESULTS: Through simulation, it is found that the pharmacokinetic parameters cmax, tmax, AUC0-∞ obtained by the two models are close to the measured values, which are all within the scope of the literature. It can be considered that the parameter conversion formulas of the two models are correct. Further, the relative deviation and relative standard error of the parameters are calculated, and the relative deviation and relative standard error of the adult-pediatric PBPK prediction model are smaller than those of the allometric growth model. CONCLUSION: The azithromycin PBPK model predicts that children's pharmacokinetic parameters are better than the allometric growth model. The scaling formula for the specific parameters of the oral-dose adult-child model used in this article, which was successfully verified by azithromycin, can be extrapolated to other drugs to facilitate the conversion of other oral-adulterated adult-pediatric models.