Key result
Co-administration of Astragalus injection and doxorubicin altered DOX pharmacokinetics and significantly inhibited the activity of CYP1A2, CYP2C9, CYP2E1, and CYP3A4 (p < 0.05).
Why the study?
Astragalus injection is combined with doxorubicin to improve efficacy and reduce resistance, but the pharmacokinetic interaction and mechanism required investigation.
p-value: p=< 0.05
Co-administration of Astragalus injection alters the systemic exposure of doxorubicin by affecting its metabolism and CYP450 enzyme activity in a rat model.
May alter DOX exposure via CYP450 in rats; leaves open clinical relevance pending human pharmacokinetic data.
BACKGROUND: Doxorubicin (DOX) is a widely used anthracycline antibiotic for the treatment of breast cancer, liver cancer, lymphoma, and other malignant tumors. However, its clinical application is limited by the side effects and drug resistance. Astragalus injection has been combined with DOX in the treatment of cancer, which improves the curative effect and reduces drug resistance. This study investigated the interaction between DOX and Astragalus injection and elucidated the potential mechanism. METHODS: The pharmacokinetics of DOX injection (7 mg/kg, intraperitoneal injection) with or without Astragalus injection (4.25 mL/kg/day for 14 days, intraperitoneal injection) were investigated in plasma from male Sprague-Dawley rats (n = 6) by UPLC-MS/MS. The group without the Astragalus injection was set as the control group. Additionally, the effects of Astragalus injection on CYP450 enzyme activities were assessed using a rat liver microsome incubation system with cocktail probe drugs. RESULTS: (1190.23 ± 104.43 vs. 3777.27 ± 130.55 μg/L × h) and prolonged the t1/2α (0.09 ± 0.02 vs. 0.14 ± 0.04 h) of DOX. Astragalus injection significantly inhibited the activity of CYP1A2, CYP2C9, CYP2E1, and CYP3A4, and enhanced the activity of CYP2D1 with a metabolic elimination rate of 30.11 ± 2.67% vs. 19.66 ± 3.41%, 35.95 ± 2.57% vs. 23.26 ± 3.57%, 13.43 ± 2.56% vs. 9.06 ± 2.51%, 47.90 ± 6.30% vs. 25.87 ± 2.55%, 17.62 ± 1.49% vs. 24.12 ± 2.91%, respectively (p < 0.05). CONCLUSION: The co-administration of DOX and Astragalus injection alters the systemic exposure of DOX by affecting the metabolism of DOX and the activity of CYP450 enzymes. These findings highlight the importance of drug-drug interactions when combining Astragalus injection with DOX and provide a basis for optimizing combination therapies to address DOX resistance and toxicity.
No takes yet. Share an insight, caveat, or question.
Shi et al. (2025) studied Pharmacokinetics of Doxorubicin (n=6). Astragalus injection vs. Doxorubicin alone was evaluated on Pharmacokinetics of DOX and CYP450 enzyme activities (p=< 0.05). Co-administration of Astragalus injection and doxorubicin altered DOX pharmacokinetics and significantly inhibited the activity of CYP1A2, CYP2C9, CYP2E1, and CYP3A4 (p < 0.05).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: