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      Lower clearance of sodium tanshinone IIA sulfonate in coronary heart disease patients and the effect of total bilirubin: a population pharmacokinetics analysis

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          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 –1 was 48.7 L·h –1 with inter individual variability of 27.4%, whereas that in healthy volunteers with the same TBIL level was 63.1 L·h –1. 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.

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          Author and article information

          Chinese Journal of Natural Medicines
          20 March 2019
          : 17
          : 3
          : 218-226
          1 Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, 200040, China
          2 Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, 200040, China
          Author notes
          *Corresponding author: JIAO Zheng, Tel: 86-21-52888712, E-mail: zjiao@ ; WANG Bin, Tel: 86-21-52888379, E-mail: wangbin@

          ΔThese authors contributed to the work equally.

          These authors have no conflict of interest to declare.

          Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funded by: Science and Technology Commission of Shanghai Municipality
          Award ID: 12DZ1930300
          Award ID: 12DZ1930302
          Award ID: 12DZ1930303
          Funded by: Weak Discipline Construction Project
          Award ID: 2016ZB0301-01
          This work was supported by the Science and Technology Commission of Shanghai Municipality (12DZ1930300, 12DZ1930302, 12DZ1930303), the Weak Discipline Construction Project (No. 2016ZB0301-01), and the 2016 Key Clinical Program of Clinical Pharmacy of Shanghai Municipal Commission of Health and Family Planning.


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