Development of a physiologically-based pharmacokinetic model for cyclosporine in Asian children with renal impairment
10.12793/tcp.2019.27.3.107
- Author:
Sumin YOON
1
;
Sojeong YI
;
Su jin RHEE
;
Hyun A LEE
;
Yun KIM
;
Kyung Sang YU
;
Jae Yong CHUNG
Author Information
1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Cyclosporine;
Ethnicity;
PBPK;
Pediatrics;
Renal impairment
- MeSH:
Adult;
Asian Continental Ancestry Group;
Child;
Cyclosporine;
Humans;
Kidney Diseases;
Pediatrics;
Pharmacokinetics
- From:Translational and Clinical Pharmacology
2019;27(3):107-114
- CountryRepublic of Korea
- Language:English
-
Abstract:
This study aimed to assess the pharmacokinetics of cyclosporine A (CsA) in Asian children with renal impairment (RI) by developing a physiologically-based pharmacokinetic (PBPK) model with Simcyp Simulator. The PBPK model of Asian children with RI was developed by modifying the physiological parameters of the built-in population libraries in Simcyp Simulator. The ratio of healthy and RI populations was obtained for each parameter showing a difference between the populations. Each ratio was multiplied by the corresponding parameter in healthy Asian children. The model verification was performed with published data of Korean children with kidney disease given multiple CsA administrations. Simulations were performed with different combinations of ethnicity, age, and renal function to identify the net impact of each factor. The simulated results suggested that the effect of RI was higher in children than adults for both Caucasian and Asian. In conclusion, the constructed model adequately characterized CsA pharmacokinetics in Korean children with RI. Simulations with populations categorized by ethnicity, age, and renal function enabled to assess the net impact of each factor on specific populations.
