A pharmacokinetic study of sodium tanshinone IIA sulfonate in coronary heart disease patients vs. healthy people

In this study, researchers from Fudan University in China developed a pharmacokinetic model for sodium tanshinone IIA sulfonate (STS) based on healthy volunteers and patients with coronary heart disease (CHD). The details of this developmental study were published in the Chinese Journal of Natural Medicines.

• STS is a water-soluble derivative of tanshinone IIA from the root of red sage (Salvia miltiorrhiza).
• The researchers wished to identify significant covariates for the pharmacokinetics of STS. They obtained blood samples from 10 healthy volunteers and 25 CHD patients using intense sampling approach and sparse sampling, respectively.
• They performed a population pharmacokinetic analysis by non-linear mixed-effect modeling.
• The researchers evaluated the final model — a two-compartment model with first-order elimination — by bootstrap and visual predictive check. This included a total of 230 plasma concentrations, 137 from healthy volunteers and 93 from CHD patients.
• They reported that the typical value of the apparent clearance (CL) of STS in CHD patients was 48.7 liters per hour (L/h), with total bilirubin (TBIL) of 10 micromol per liter (umol/L). Individual variability was 27.4 percent.
• Meanwhile, in healthy volunteers with the same TBIL level, the CL of STS was 63.1 L/h.
• The researchers described residual variability by a proportional error model and estimated it at 5.2 percent.
• They also reported that the CL of STS in CHD patients was lower than that in healthy volunteers, and decreased as TBIL levels increased.
• They confirmed the stability and validity of the final model using the bootstrap and visual predictive check.

Based on these results, the researchers concluded that STS dosage adjustment should be considered based on the TBIL levels of CHD patients.

Journal Reference:

Qin WW, Wang L, Jiao Z, Wang B, Wang CY, Qian LX, Qi WL, Zhong MK. LOWER CLEARANCE OF SODIUM TANSHINONE IIA SULFONATE IN CORONARY HEART DISEASE PATIENTS AND THE EFFECT OF TOTAL BILIRUBIN: A POPULATION PHARMACOKINETICS ANALYSIS. Chinese Journal of Natural Medicines. March 2019;17(3):218–226. DOI: 10.1016/s1875-5364(19)30024-x