Comparative Pharmacokinetics of Six Bioactive Constituents From Danggui Jixueteng Decoction in Normal and Myelosuppressive Rats

Abstract

This study compared the pharmacokinetics of six constituents from Danggui Jixueteng Decoction in normal versus carboplatin-induced myelosuppressive rats. A rapid, sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous quantification of six diverse constituents (8-O-debenzoylpaeoniflorin, ferulic acid, calycosin, albiflorin, oxypeucedanin hydrate and neocryptotanshinone) in rat plasma, and applied for the first time to compare pharmacokinetics under normal and diseased states. Male Sprague-Dawley rats received oral decoction (12.42 g/kg daily, 7 days) after myelosuppression induction by intraperitoneal carboplatin. Serial blood samples were collected after the final dose and analysed. In model rats, systemic exposure to calycosin increased significantly, with elevated area under the curve (AUC_0–∞) and maximum concentration (C_max) (p < 0.05), along with a shortened T_max. 8-O-Debenzoylpaeoniflorin showed a trend towards increased exposure, though the differences did not reach statistical significance. Conversely, neocryptotanshinone showed reduced AUC_0–∞ and C_max, delayed T_max, and a significantly shorter elimination half-life (p < 0.05). Ferulic acid exposure remained stable, but its half-life shortened significantly (p < 0.05). Albiflorin and oxypeucedanin hydrate were minimally affected. Myelosuppression selectively alters the in vivo disposition of the formula constituents, supporting its use as an adjunctive therapy during chemotherapy.