AUTHOR=Chen Xiao , Wang Jinglin , Lan Jianger , Ge Xilin , Xu Hong , Zhang Yu , Li Zhiping TITLE=Initial sirolimus dosage recommendations for pediatric patients with PIK3CD mutation-related immunodeficiency disease JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.919487 DOI=10.3389/fphar.2022.919487 ISSN=1663-9812 ABSTRACT=

Sirolimus is used to treat pediatric patients with PIK3CD mutation-related immunodeficiency disease. However, the initial dosages of sirolimus remain undecided. The present study aims to explore initial dosages in pediatric patients with PIK3CD mutation-related immunodeficiency disease. Pediatric patients with this disease were analyzed using the population pharmacokinetic (PPK) model and the Monte Carlo simulation. Body weight and concomitant use of posaconazole were included in the final PPK model, where, under the same weight, clearances of sirolimus were 1 : 0.238 between children without and children with posaconazole. Without posaconazole, the initial dosages of sirolimus were 0.07, 0.06, 0.05, and 0.04 mg/kg/day for body weights of 10–14, 14–25, 25–50, and 50–60 kg, respectively. With posaconazole, the initial dosages of sirolimus were 0.02 mg/kg/day for body weights of 10–60 kg. This is the first attempt to build a sirolimus PPK model for recommending initial dosages in children with PIK3CD mutation-related immunodeficiency disease, thereby providing a reference for individualized clinical drug administration.