title: Rifampin enhances the glucose-lowering effect of metformin and increases OCT1 mRNA levels in healthy participants.
abstract: We evaluated the effect of the pregnane X receptor (PXR) agonist rifampin on metformin pharmacokinetics, organic cation transporter 1 (OCT1) and OCT2 mRNA levels, and glucose levels, using the oral glucose tolerance test (OGTT) in 16 healthy subjects. The glucose-lowering effects of metformin were evaluated by OGTT before and after metformin treatment on days 1 and 2 and again on days 13 and 14 after a 10-day course of rifampin. Rifampin increased the difference in maximum glucose levels (ΔG(max)) by 41.9% (P = 0.024) and the area under the concentration-time curve (AUC) during the first 60 min after glucose ingestion (ΔAUC(gluc60)) by 54.5% (P = 0.020). Renal clearance (CL(R)) of metformin was increased by 16% (P = 0.008), but the systemic exposure was only slightly increased (13%, P = 0.049), possibly because of increased absorption. Rifampin increased OCT1 mRNA levels 4.1-fold in peripheral blood cells (P = 0.001); however, OCT2 mRNA was not detected. Our results suggest that rifampin increases OCT1 expression and hepatic uptake of metformin, leading to enhanced glucose-lowering action.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Cho
authors.forename: J S
authors.initials: JS
authors.lastname: Yoon
authors.forename: M G
authors.initials: MG
authors.lastname: Lee
authors.forename: D H
authors.initials: DH
authors.lastname: Lee
authors.forename: L A
authors.initials: LA
authors.lastname: Lim
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: M S
authors.initials: MS
authors.lastname: Park
authors.forename: J-Y
authors.initials: JY
authors.lastname: Chung
mesh_terms: D000328:Adult; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics* / Q000494:pharmacology; D050811:Octamer Transcription Factor-1 / Q000187:drug effects / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000187:drug effects / Q000235:genetics*; D000075102:Organic Cation Transporter 2; D000077297:Pregnane X Receptor; D011446:Prospective Studies; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011987:Receptors, Steroid / Q000819:agonists; D012293:Rifampin / Q000494:pharmacology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D050811:Octamer Transcription Factor-1; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; C491013:SLC22A2 protein, human; D008687:Metformin; D012293:Rifampin