title: Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein- and cytochrome P4503A-mediated herb-drug interactions.
abstract: 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.
authors.affiliation: College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Shin
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Oh
authors.forename: Young Pyo
authors.initials: YP
authors.lastname: Jang
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077144:Clopidogrel; D016572:Cyclosporine / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects* / Q000378:metabolism; D000077143:Docetaxel; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D007262:Infusions, Intravenous; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D010975:Platelet Aggregation Inhibitors; D043823:Taxoids; D000077143:Docetaxel; C028972:dan-shen root extract; D016572:Cyclosporine; D000077144:Clopidogrel; D051544:Cytochrome P-450 CYP3A; D013988:Ticlopidine