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.
He
Ju-Xiu
JX
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Akao
Teruaki
T
Tani
Tadato
T
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