title: Effect of a Kampo preparation, byakkokaninjinto, on pharmacokinetics of ciprofloxacin and tetracycline.
abstract: The effect on the bioavailability of the antimicrobial agents (ciprofloxacin and tetracycline), which are well known to form chelates with cationic metals such as calcium, was evaluated in 20 healthy male volunteers according to an open, random crossover fashion using a Kampo preparation, byakkokaninjinto (TJ-34) which contains various cationic metals including calcium. Each subject received a single oral dose of tetracycline (250 mg) alone or ciprofloxacin (200 mg) alone along with a single coadministration of one pack (3 g) of the Kampo preparation, at one-week intervals. Concentrations of the drugs in plasma and urine were analyzed by HPLC. Concomitant administration of the Kampo preparation significantly decreased the peak plasma concentration (C(max)) and area under the plasma concentration-time curves (AUC), but not time to reach C(max) (T(max)), of ciprofloxacin and tetracycline. However, the decrease in bioavailability of ciprofloxacin was slight (15%) compared with that of tetracycline (30%). The Kampo preparation significantly decreased the urinary recovery of tetracycline, but not ciprofloxacin, and it had no effect on the renal clearance of either ciprofloxacin or tetracycline. These results indicate that the Kampo preparation tested in this study reduces the extent of bioavailability of ciprofloxacin and tetracycline, but not renal excretion, by decreasing the gastrointestinal absorption due to the formation of insoluble chelates with calcium. We recommend that the dose timing of the Kampo preparation should be carefully controlled to avoid therapeutic failure especially for patients receiving the treatment with tetracycline.
authors.affiliation: Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine, Aichi, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hitoshi
authors.forename: Miki
authors.initials: M
authors.lastname: Katoh
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nadai
authors.forename: Fumie
authors.initials: F
authors.lastname: Abe
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kurono
authors.forename: Hiroko
authors.initials: H
authors.lastname: Saito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Haniuda
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020835:Medicine, Kampo; D013752:Tetracycline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004365:Drugs, Chinese Herbal; C108060:byakko-ka-ninjin-to; D002939:Ciprofloxacin; D013752:Tetracycline