Pharmacokinetic–pharmacodynamic modeling of the active components of Shenkang injection in rats with chronic renal failure and its protective effect on damaged renal cells

The study aimed to explore the pharmacokinetic and pharmacodynamic alterations of the active components of Shenkang injection (i.e. hydroxy saffron yellow pigment A [HSYA], tanshinol, rheum emodin, and astragaloside IV) in rats with chronic renal failure (CRF), and establish a pharmacokinetic–pharmacodynamic model (PK‐PD model) in order to provide a scientific and theoretical basis for the rational clinical use of Shenkang injection. Sprague–Dawley (SD) rats were randomly divided into a normal group, model group, and Shenkang injection group. A rat model of CRF was induced by adenine gavage and then followed by drug administration via tail vein injection. Orbital blood was collected at different timepoints and the blood concentrations of the four active components were measured by UHPLC‐Q‐Orbitrap HRMS. Serum levels of creatinine (Scr), urea nitrogen (BUN), and uric acid (UA) were determined using an automatic biochemical analyzer. A PK‐PD model was established, and DAS 3.2.6 software was used for model fitting as well as statistical analysis. TGF‐β1 was utilized to induce normal rat kidney cells to construct a renal fibrosis model to investigate the protective effect of the pharmacological components on renal fibrosis. The pharmacokinetic analysis of hydroxy saffron yellow pigment A, tanshinol, rheum emodin, and astragaloside IV based on UHPLC‐Q‐Orbitrap HRMS was stable. The linear regression equations for the four active components were as follows: Y = 0.031X + 0.0091 ( R 2 = 0.9986) for hydroxy saffron yellow pigment A, Y = 0.0389X + 0.164 ( R 2 = 0.9979) for tanshinol, Y = 0.0257X + 0.0146 ( R 2 = 0.9973) for rheum emodin, and Y = 0.0763X + 0.0139 ( R 2 = 0.9993) for astragaloside IV, which indicated good linear relationships. The methodological investigation was stable, with the interday and intraday precision RSD