Mechanism of drug interaction between a Kampo medicine, byakkokaninjinto, and tetracycline in rats

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 18; no. 1; pp. 75 - 82
• Main Authors: Hitoshi, Kotaro, Katoh, Miki, Tanaka, Yoshiteru, Kurono, Shunsuke, Nadai, Masayuki, Hotta, Kazuo, Saito, Hiroko, Hasegawa, Takaaki
• Format: Journal Article
• Language: English
• Published: Japan Elsevier Ltd 01.02.2012; Springer Japan
• Subjects: Animals; Biological Availability; Byakkokaninjinto; Chelate; Drug Administration Schedule; Drug interaction; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Edetic Acid - pharmacology; Hematology, Oncology and Palliative Medicine; Herb-Drug Interactions; Infectious Diseases; Kampo medicine; Male; Medical Microbiology; Medicine; Medicine & Public Health; Medicine, Kampo; Original Article; Rats; Rats, Wistar; Tetracycline; Tetracycline - pharmacokinetics; Tetracycline - pharmacology; Virology; Byakkokaninjinto; Drug interaction; Kampo medicine; Chelate; Tetracycline
• ISSN: 1341-321X; 1437-7780
• DOI: 10.1007/s10156-011-0294-2

Abstract We have previously reported that concomitant oral administration of the Kampo medicine, byakkokaninjinto (TJ-34), in extract granules, reduced the plasma concentrations of tetracycline (TC) and ciprofloxacin in humans, which might be the result of forming a chelate with Ca2+ . In the present study, we investigated the effect of a chelating agent, ethylenediaminetetraacetic acid (EDTA), on the plasma concentration–time profiles of TC after coadministration of TJ-34 dried extract and TC in rats to clarify whether metal ions contained in the TJ-34 dried extract contribute to this interaction. TJ-34 dried extract significantly reduced the plasma concentration of TC. The values of maximum concentration ( Cmax ), area under the plasma concentration–time curve and percentage of urinary recovery ( fe ) of TC were reduced to 42%, 40%, and 45%, respectively. On the other hand, treatment with EDTA significantly counteracted the effect of TJ-34 dried extract to reduce absorption of TC, indicating that metal ions mainly account for the interaction. Next, we investigated the effect of staggered administration of TJ-34 dried extract and TC to avoid the drug interaction between them. Administration of TJ-34 dried extract 2 h before TC had no effect on plasma concentrations and pharmacokinetic parameters of TC. These results provide a precise mechanism of the interaction TJ-34 and TC, suggesting a safe and effective dosage regimen to coadminister TJ-34 and TC in clinical use.