Population pharmacokinetic study of tacrolimus in pediatric patients with primary nephrotic syndrome
10.16438/j.0513-4870.2017-0639
- VernacularTitle:儿童原发性肾病综合征患者中他克莫司的群体药动学研究
- Author:
Ling-fei HUANG
1
;
Chen-yan ZHAO
2
;
Zheng JIAO
2
;
Yi-xi LIU
2
;
Hui-fen ZHANG
1
;
Jue WANG
1
;
Jian-hua MAO
3
Author Information
1. Department of Pharmacy, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
2. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China
3. Department of Nephrology, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
tacrolimus;
children;
primary nephrotic syndrome;
population pharmacokinetic;
nonlinear mixed effect model
- From:
Acta Pharmaceutica Sinica
2018;53(2):263-270
- CountryChina
- Language:Chinese
-
Abstract:
Tacrolimus is commonly used in the treatment for the refractory primary nephrotic syndrome (PNS) in the pediatric patients. Data were retrospectively obtained from 100 children with 357 tacrolimus trough concentrations in our center between May 2010 and March 2016. Information of age, sex, body weight, drug dose, co-therapy medications, laboratory tests and sampling time were collected. The population pharmacokinetic model was developed using nonlinear mixed effect modeling (NONMEM) software. A one-compartment model with first-order absorption and elimination best described the data. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 6.54 L·h-1 and 86.2 L, respectively. Body weight (WT, kg), daily dose of tacrolimus (DD, mg·day-1) and co-therapy azole antifungal agent have a significant impact on the CL/F. The final PPK model of CL/F was:CL/F=6.54×((WT)/25)K×((DD)/1.5)0.293×0.657Azole,K=(WT-30.9)/(WT-30.9+10.4-30.9). When combined with azole antifungal agents, Azole was 1, whereas vice versa was 0. This is the first PPK study of tacrolimus conducted in pediatric patients with PNS, which may facilitate individualized drug therapy of tacrolimus.
