Influence of co-administered antibiotics on the pharmacokinetic fate in rats of paeoniflorin and its active metabolite paeonimetabolin-I from Shaoyao-Gancao-tang.
The effects of orally co-administered antibiotics on the pharmacokinetics of paeoniflorin (PF) and paeonimetabolin-I (PM-I), a bioactive metabolite derived from PF by intestinal bacteria, from the traditional Chinese formulation, Shaoyao-Gancao-tang (SGT), were investigated in rats to clarify the effect of administering SGT together with some synthetic drugs. Co-administration of the antibiotics amoxicillin and metronidazole (AMPC-MET) significantly increased the area under the plasma concentration versus time curve (AUC) of PF, whereas it markedly decreased that of PM-I, to 2.6% of the normal AUC by administration of a single dose, and less than 1% by a 3-day pretreatment. Similar effects were observed using the combination of ofloxacin with SGT. The PF-metabolizing activity of intestinal bacteria was reduced to 16% and 33% of normal levels by treatment with AMPC-MET and ofloxacin, respectively, which caused alterations of that degree in the extent of absorption of PF and PM-I, but did not affect their rate of absorption or elimination. The present study suggests that it may not be appropriate to use SGT simultaneously with antibiotics such as AMPC-MET or ofloxacin, and also reveals the important role of intestinal bacteria in the pharmacokinetics of the active components of this traditional Chinese formulation.
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Ju-Xiu
JX
He
Teruaki
T
Akao
Tadato
T
Tani
D000658:Amoxicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology; D019540:Area Under Curve; D001565:Benzoates / Q000493:pharmacokinetics*; D001711:Biotransformation; D001952:Bridged-Ring Compounds / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D005243:Feces / Q000382:microbiology; D005960:Glucosides / Q000493:pharmacokinetics*; D008297:Male; D020835:Medicine, Kampo; D008795:Metronidazole / Q000494:pharmacology; D039821:Monoterpenes; D015242:Ofloxacin / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D006027:Glycosides
D000658:Amoxicillin; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001565:Benzoates; D001952:Bridged-Ring Compounds; D004338:Drug Combinations; D005960:Glucosides; D008795:Metronidazole; D039821:Monoterpenes; D015242:Ofloxacin; D010406:Penicillins; C015423:peoniflorin; D006027:Glycosides; C106915:paeonimetabolin I