title: Mechanism of drug interaction between a Kampo medicine, byakkokaninjinto, and tetracycline in rats.
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 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.
authors: Department of Pharmaceutics, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya, 468-8503, Japan.
authors: Kotaro
authors: K
authors: Hitoshi
authors: Miki
authors: M
authors: Katoh
authors: Yoshiteru
authors: Y
authors: Tanaka
authors: Shunsuke
authors: S
authors: Kurono
authors: Kazuo
authors: K
authors: Hotta
authors: Hiroko
authors: H
authors: Saito
authors: Takaaki
authors: T
authors: Hasegawa
authors: Masayuki
authors: M
authors: Nadai
mesh_terms: D000818:Animals; D001682:Biological Availability; D004334:Drug Administration Schedule; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D041743:Herb-Drug Interactions; D008297:Male; D020835:Medicine, Kampo; D051381:Rats; D017208:Rats, Wistar; D013752:Tetracycline / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D004365:Drugs, Chinese Herbal; C108060:byakko-ka-ninjin-to; D004492:Edetic Acid; D013752:Tetracycline