Drug-drug interaction between danshensu and irbesartan and its potential mechanism

Xenobiotica. 2024 Apr 9:1-9. doi: 10.1080/00498254.2024.2338183. Online ahead of print.ABSTRACT1. To uncover the effect of danshensu on irbesartan pharmacokinetics and its underlying mechanisms.2. To investigate the effect of danshensu on the pharmacokinetics of irbesartan, Sprague-Dawley rats (n = 6) were orally administered 30 mg/kg irbesartan alone (control group) or pretreated with 160 mg/kg danshensu (experimental group). The effect of danshensu on the metabolic stability of irbesartan in RLMs was examined by LC-MS/MS method. The effect of danshensu on CYP2C9 activity was also determined.3. Danshensu markedly increased the AUC(0-t) (9573 ± 441 vs. 16157 ± 559 μg/L*h) and Cmax (821 ± 24 vs. 1231 ± 44 μg/L) of irbesartan. Danshensu prolonged the t1/2 (13.39 ± 0.98 vs. 16.04 ± 1.21 h) and decreased the clearance rate (2.27 ± 0.14 vs. 1.19 ± 0.10 L/h/kg) of irbesartan. Danshensu enhanced the metabolic stability of irbesartan in vitro with prolonged t1/2 (36.34 ± 11.68 vs. 48.62 ± 12.03 min) and reduced intrinsic clearance (38.14 ± 10.24 vs. 28.51 ± 9.06 μL/min/mg protein). Additionally, the IC50 value for CYP2C9 inhibition by danshensu was 35.74 μM.4. Danshensu enhanced systemic exposure of irbesartan by suppressing CYP2C9. The finding can also serve as a guidance for further investigation of danshensu-irbesartan interaction in clinical practice.PMID:38591142 | DOI:10.1080/00498254.2024.2338183

Source: Xenobiotica - April 9, 2024 Category: Research Authors: Yuexia Li Liheng Liu Source Type: research