Lower clearance of sodium tanshinone IIA sulfonate in coronary heart disease patients and the effect of total bilirubin: a population pharmacokinetics analysis.
10.1016/S1875-5364(19)30024-X
- Author:
Wei-Wei QIN
1
;
Li WANG
1
;
Zheng JIAO
2
;
Bin WANG
3
;
Cheng-Yu WANG
1
;
Li-Xuan QIAN
1
;
Wei-Lin QI
4
;
Ming-Kang ZHONG
1
Author Information
1. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China.
2. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address: zjiao@fudan.edu.cn.
3. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China. Electronic address: wangbin@huashan.org.cn.
4. Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
- Publication Type:Journal Article
- Keywords:
Coronary heart disease;
Nonlinear mixed-effects modeling;
Population pharmacokinetics;
Sodium tanshinone IIA sulfonate;
Total bilirubin
- MeSH:
Adult;
Aged;
Aged, 80 and over;
Bilirubin;
blood;
Coronary Disease;
drug therapy;
metabolism;
Drugs, Chinese Herbal;
administration & dosage;
pharmacokinetics;
Female;
Humans;
Male;
Metabolic Clearance Rate;
Middle Aged;
Models, Biological;
Phenanthrenes;
administration & dosage;
blood;
pharmacokinetics
- From:
Chinese Journal of Natural Medicines (English Ed.)
2019;17(3):218-226
- CountryChina
- Language:English
-
Abstract:
This study developed a population pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) in healthy volunteers and coronary heart disease (CHD) patients in order to identify significant covariates for the pharmacokinetics of STS. Blood samples were obtained by intense sampling approach from 10 healthy volunteers and sparse sampling from 25 CHD patients, and a population pharmacokinetic analysis was performed by nonlinear mixed-effect modeling. The final model was evaluated by bootstrap and visual predictive check. A total of 230 plasma concentrations were included, 137 from healthy volunteers and 93 from CHD patients. It was a two-compartment model with first-order elimination. The typical value of the apparent clearance (CL) of STS in CHD patients with total bilirubin (TBIL) level of 10 μmol(L was 48.7 L(h with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L(h. Residual variability was described by a proportional error model and estimated at 5.2%. The CL of STS in CHD patients was lower than that in healthy volunteers and decreased when TBIL levels increased. The bootstrap and visual predictive check confirmed the stability and validity of the final model. These results suggested that STS dosage adjustment might be considered based on TBIL levels in CHD patients.
