Pharmacokinetics and tissue distribution study of 18 bioactive components in healthy and chronic heart failure rats after oral administration of Qi-Shen-Ke-Li formula using ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry.

Abstract

Qi-Shen-Ke-Li (QSKL) is a traditional Chinese formula used in clinical practice to treat chronic heart failure (CHF) in humans. To rationalize the use of this formula in clinical practice, the pharmacokinetics and tissue distribution in rats after oral administration of QSKL were investigated using ultra-high-performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC/TQ-MS). The CHF model was induced by intraperitoneal injection of isoprenaline (ISO; also known as isoproterenol) and evaluated by HE staining and brain natriuretic peptide (BNP) measurement. The UHPLC/TQ-MS method was then applied to determine the concentrations of 18 bioactive components in rat plasma and tissues of heathy and CHF rats after oral administration of QSKL. This was followed by investigating the pharmacokinetics and tissue distribution profiles of these bioactive compounds in the heathy and CHF rats. The pharmacokinetics results showed that the duration time of two compounds was prolonged, the absorption rate of four compounds was accelerated, and the bioavailability of four compounds was increased in the CHF rats compared with the healthy rats. Meanwhile, the tissue distribution results showed that the QSKL formula could be distributed rapidly and widely in different rat tissues. The bioavailability of eight compounds in the liver was enhanced in CHF rats. This suggested that the drug/toxic effects should be considered in clinical practice, as drug-drug interactions might occur in liver metabolism during the drug combination. The pharmacokinetic profiles and tissue distribution of 18 bioactive compounds in QSKL are altered by the CHF status. This study provides insight for better clinical applications of this formula in the future and lays the foundation for the development of a new drug for chronic heart failure based on the QSKL formula.