Pharmacokinetic interactions between metformin and berberine in rats: Role of oral administration sequences and microbiota
Publication in refereed journal


Times Cited
Altmetrics Information
.

Other information
AbstractAIMS:
Considering the potential oral administration sequences and role of microbiota for metformin (MET) and berberine (BBR) during anti-diabetic treatments, the current study aimed to investigate the pharmacokinetic interactions between MET and BBR in rats after oral administration at different sequences and impacts of microbiota on such interactions.

MAIN METHODS:
Sprague-Dawley rats were divided into five groups as per what was orally administered to them: MET (G1)/BBR (G2) at 200 mg/kg, BBR 2-hour (h) after dosing MET (G3), MET 2-h after dosing BBR (G4) or MET with BBR at the same time (G5) followed by monitoring their pharmacokinetic profiles. Further in vitro incubations mimicking the above five treatments in rat intestinal content (G1R-G5R), human fecalase (G1H-G5H) and selected bacteria (G1B-G5B) were conducted for both MET and BBR (10 μg/ml for G1R/H-G5R/H and 50 μM for G1B-G5B) up to 24-h. Concentrations of MET and BBR were analyzed by LC/MS/MS.

KEY FINDINGS:
Although BBR was barely measurable in vivo, it significantly increased systemic exposure of MET in G3/G4. Consistent with pharmacokinetic findings, sequential in vitro incubations of MET and BBR in both rat intestinal content and human fecalase demonstrated significant increase on MET persisted after 24-h incubation in G3R/H & G4R/H. Moreover, post-dose (G3B) and pre-dose (G4B) of BBR decreased the MET degradation significantly in most selected bacteria.

SIGNIFICANCE:
Our finding for the first time demonstrated the significant effect of sequential co-administration of BBR and MET on their pharmacokinetic interactions, which could be related to their microbiota mediated metabolisms in gastrointestinal tract (GI).
All Author(s) ListYuanfeng Lyu, Yufeng Zhang, Mengbi Yang, Lin Lin, Xiao Yang, Stanley Chun Kai Cheung, Pang Chui Shaw, Paul Kay Sheung Chan, Alice Pik Shan Kong, Zhong Zuo
Journal nameLife Sciences
Year2019
Month10
Day15
Volume Number235
Article number116818
ISSN0024-3205
LanguagesEnglish-United States

Last updated on 2020-17-09 at 00:16