title: The Relation between Hepatotoxicity and the Total Coumarin Intake from Traditional Japanese Medicines Containing Cinnamon Bark.
abstract: Cinnamon bark is commonly used in traditional Japanese herbal medicines (Kampo medicines). The coumarin contained in cinnamon is known to be hepatotoxic, and a tolerable daily intake (TDI) of 0.1 mg/kg/day, has been quantified and used in Europe to insure safety. Risk assessments for hepatotoxicity by the cinnamon contained in foods have been reported. However, no such assessment of cinnamon bark has been reported and the coumarin content of Kampo medicines derived from cinnamon bark is not yet known. To assess the risk for hepatotoxicity by Kampo medicines, we evaluated the daily coumarin intake of patients who were prescribed Kampo medicines and investigated the relation between hepatotoxicity and the coumarin intake. The clinical data of 129 outpatients (18 male and 111 female, median age 58 years) who had been prescribed keishibukuryogankayokuinin (TJ-125) between April 2008 and March 2013 was retrospectively investigated. Concurrent Kampo medicines and liver function were also surveyed. In addition to TJ-125, the patients took some of the other 32 Kampo preparations and 22 decoctions that include cinnamon bark. The coumarin content of these Kampo medicines was determined by high performance liquid chromatography (HPLC). TJ-125 had the highest daily content of coumarin (5.63 mg/day), calculated from the daily cinnamon bark dosage reported in the information leaflet inserted in each package of Kampo medicine. The coumarin content in 1g cinnamon bark decoction was 3.0 mg. The daily coumarin intake of the patients was 0.113 (0.049-0.541) mg/kg/day, with 98 patients (76.0%) exceeding the TDI. Twenty-three patients had an abnormal change in liver function test value, but no significant difference was found in the incidence of abnormal change between the group consuming less than the TDI value (6/31, 19.4%) and the group consuming equal to or greater than the TDI value (17/98, 17.3%). In addition, no abnormal change related to cinnamon bark was found for individual patients. This paper was done to assess the risk of hepatotoxicity by the coumarin contained in Kampo medicines and to clarify whether or not the Kampo preparations in general use that contain cinnamon bark may be safely used in clinical practice.
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Community Medicine Education Unit, Graduate School of Medical Sciences, Kyushu UniversityFukuoka, Japan; Department of General Internal Medicine, Kyushu University HospitalFukuoka, Japan.
authors.forename: Mosaburo
authors.initials: M
authors.lastname: Kainuma
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sugawara
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Uchida
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ozono
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamamuro
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital Fukuoka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: Department of Pediatrics, Matsuyama Red Cross Hospital Matsuyama, Japan.
authors.forename: Koso
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Japanese Oriental (Kampo) Medicine, Oriental Medical Center, Iizuka Hospital Iizuka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tahara
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University Fukuoka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Shimazoe
keywords: cinnamon bark; coumarin; hepatotoxicity; high performance liquid chromatography; keishibukuryogankayokuinin; tolerable daily intake; traditional Japanese herbal medicine