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

Autor: Yoshiteru Tanaka, Kazuo Hotta, Kotaro Hitoshi, Takaaki Hasegawa, Shunsuke Kurono, Masayuki Nadai, Hiroko Saito, Miki Katoh
Rok vydání: 2012
Předmět:
Zdroj: Journal of Infection and Chemotherapy. 18:75-82
ISSN: 1341-321X
DOI: 10.1007/s10156-011-0294-2
Popis: 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 Ca(2+). 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 (C (max)), area under the plasma concentration-time curve and percentage of urinary recovery (f (e)) 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.
Databáze: OpenAIRE
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