title: Pharmacokinetic interactions between warfarin and kangen-karyu, a Chinese traditional herbal medicine, and their synergistic action.
abstract: Kangen-Karyu (KGK), containing six herbs, is a formula created under the theory of Chinese traditional medicine (CTM) to invigorate the 'blood' and dispel 'blood stasis', which arises from poor blood circulation. The present study was conducted to evaluate the interactions between KGK and warfarin. Warfarin was administered orally or intravenously to KGK-treated rats, and plasma warfarin concentration and prothrombin time were measured. Although KGK did not influence the absorption or serum protein binding of warfarin, KGK significantly suppressed the metabolism and elimination of warfarin. This interaction depends on the dosage of KGK, and ten times the amount of the human daily dose of KGK did not exhibit pharmacokinetic interaction with warfarin, suggesting that KGK did not influence the effect of warfarin unless the daily dose was strictly maintained. Warfarin alone significantly prolonged mice tail-bleeding time, which was further prolonged significantly by KGK at a dose that did not exhibit pharmacokinetic interactions with warfarin, suggesting that KGK and warfarin might synergistically prevent thrombosis, and that combined use of these drugs could be therapeutically valuable. When physicians or pharmacists utilize combined therapy using warfarin and KGK, they must make a careful effort to check the coagulative status and regulate the dosage of each drug.
authors.affiliation: Department of Kampo Medicinal Science, Hokkaido College of Pharmacy, Katsuraoka, Otaru 047-0264, Japan. makino@hokuyakudai.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Makino
authors.forename: Hannosuke
authors.initials: H
authors.lastname: Wakushima
authors.forename: Takuya
authors.initials: T
authors.lastname: Okamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Okukubo
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Deguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kano
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D041743:Herb-Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D004365:Drugs, Chinese Herbal; C468270:Kangen-karyu; D014859:Warfarin