Population pharmacokinetics of tacrolimus in idiopathic membranous nephropathy patients
10.16438/j.0513-4870.2020-1073
- VernacularTitle:中国特发性膜性肾病患者他克莫司群体药动学研究
- Author:
Chuan-mei WEI
1
;
Chun-xia GOU
1
;
Kang-na CAO
2
,
3
;
Xiao-qin LIU
2
,
4
;
Fei GAO
1
;
Ting-ting LIN
1
;
Zheng JIAO
2
Author Information
1. Department of Pharmacy, Binzhou Medical University Hospital, Binzhou 256603, China
2. Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
3. Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing 211198, China
4. Huashan Hospital, Fudan University, Shanghai 200040, China
- Publication Type:Research Article
- Keywords:
idiopathic membranous nephropathy;
tacrolimus;
population pharmacokinetics;
nonlinear mixed effect modeling;
rug-drug interaction
- From:
Acta Pharmaceutica Sinica
2020;55(12):2960-2967
- CountryChina
- Language:Chinese
-
Abstract:
The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.
