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

Joo Hyun Lee; Yong-Jun Shin; Hye Jin Kim; Ju-Hee Oh; Young Pyo Jang; Young-Joo Lee

doi:10.1016/j.ijpharm.2011.03.031

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

Int J Pharm. 2011 May 30;410(1-2):68-74. doi: 10.1016/j.ijpharm.2011.03.031. Epub 2011 Mar 21.

Authors

Joo Hyun Lee¹, Yong-Jun Shin, Hye Jin Kim, Ju-Hee Oh, Young Pyo Jang, Young-Joo Lee

Affiliation

¹ College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.

PMID: 21421030
DOI: 10.1016/j.ijpharm.2011.03.031

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Administration, Oral
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / pharmacokinetics
Clopidogrel
Cyclosporine / pharmacology
Cytochrome P-450 CYP3A / drug effects*
Cytochrome P-450 CYP3A / metabolism
Docetaxel
Drugs, Chinese Herbal / pharmacology*
Herb-Drug Interactions
Infusions, Intravenous
Male
Platelet Aggregation Inhibitors / pharmacokinetics
Rats
Rats, Sprague-Dawley
Salvia miltiorrhiza / chemistry
Taxoids / administration & dosage
Taxoids / pharmacokinetics*
Ticlopidine / analogs & derivatives*
Ticlopidine / pharmacokinetics

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents
Drugs, Chinese Herbal
Platelet Aggregation Inhibitors
Taxoids
Docetaxel
dan-shen root extract
Cyclosporine
Clopidogrel
Cytochrome P-450 CYP3A
Ticlopidine