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Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein- and cytochrome P4503A-mediated herb–drug interactions

2011; Elsevier BV; Volume: 410; Issue: 1-2 Linguagem: Inglês

10.1016/j.ijpharm.2011.03.031

1873-3476

Joo Hyun Lee, Yong‐Jun Shin, Hye Jin Kim, Ju‐Hee Oh, Young Pyo Jang, Young Ju Lee,

Alkaloids: synthesis and pharmacology

Danshen (Salvia miltiorrhiza) contains tanshinones, which inhibit P-glycoprotein (P-gp) and the cytochrome P450 (CYP) system. In the present study, we evaluated the possible pharmacokinetic interactions of Danshen extract with docetaxel and clopidogrel in rats. Docetaxel (5 mg/kg intravenously and 40 mg/kg orally) or clopidogrel (30 mg/kg orally) was administered to rats with or without oral co-administration of Danshen (400 mg/kg). Co-administration of Danshen did not affect the plasma concentration profiles and pharmacokinetic parameters of docetaxel and clopidogrel, whereas cyclosporine A, a P-gp and CYP3A inhibitor, significantly influenced the pharmacokinetics of co-administered docetaxel and clopidogrel. Orally administered Danshen had no substantial effect on the pharmacokinetics of docetaxel and clopidogrel, suggesting the negligible safety concern of Danshen in P-gp- and CYP3A-mediated interactions in vivo.