There is an increase in Metformin concentration and its effect on glucose concentrations in the presence of Rifampin. However, further studies are necessary to determine relevant effects and toxicities in patients with Tuberculosis and Diabetes.
Rifampin Versus Metformin
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Study Design
This study evaluated the interaction between Rifampin and Metformin by comparing glucose levels using 3-hour oral glucose tolerance tests (OGTTs, 75 grams of glucose) in 16 healthy volunteers (fasting glucose, 90 ± 8 mg/dl) before and after Metformin treatment (1,750 mg total) on days 1 and 2 and again on days 13 and 14, after a 10-day course of rifampin (600 mg daily). OCT1 and OCT2 mRNA levels were determined using real-time PCR. Blood and urine samples were also collected to compare the ability of metformin to reduce maximum blood glucose levels (∆Gmax) and to measure the area under the curve of glucose concentration–time (AUC of glucose) during the first 60 min after glucose ingestion (∆AUCgluc60) and the AUC of glucose for the entire 180-min test before and after rifampin treatment.
Study Results
Rifampin treatment increased the mean value of ∆Gmax by 41.9% (31 vs. 44 mg/dl; P = 0.024) and that of ∆AUCgluc60 by 54.5% (914 ± 510 mg/dl·min vs. 1,412 ± 555 mg/dl·min; P = 0.020). Moreover, after rifampin treatment, metformin plasma concentrations were 23% higher at 0.5 h (P = 0.002) and 13% higher at 1 h (P = 0.036). The AUC for the full 24 h (AUCmet(0–24h)) increased 13% after rifampin treatment (9,408 ± 2,410 vs. 10,672 ± 3,149 ng/ml·h, P = 0.049), whereas Cmax was not significantly different (1,536 ± 350 vs. 1,692 ± 114 ng/ml, P = 0.070). Rifampin treatment did not significantly alter the half-time (t1/2) of metformin, but it increased the renal clearance of metformin by 16% (501 ± 97 vs. 580 ± 101 ml/min, P = 0.008). Consistent with the rifampin-enhanced glucose tolerance, OCT1 mRNA levels were 4.1-fold higher after rifampin treatment (410 ± 260%, P = 0.001).
Study Conclusions
This study found that rifampin increased the concentration of metformin in the blood and enhanced its glucose-lowering action. Rifampin–metformin interactions in patients with tuberculosis or type 2 diabetes may affect drug safety as well as efficacy because the most toxic side effect of metformin, lactic acidosis, is dose-dependent. Moreover, OCT1 plays an important role in metformin uptake and action in the liver; therefore, the increased OCT1 mRNA levels suggest that rifampin enhances the glucose-lowering action of metformin by upregulating OCT1. Further study is necessary to confirm OCT-based drug interactions in patients with tuberculosis and type 2 diabetes who are receiving both rifampin and metformin.
References
Cho SK, Yoon JS, Lee MG. Rifampin enhances the glucose-lowering effect of metformin and increases oct1 mrna levels in healthy participants. Clinical Pharmacology & Therapeutics. 2011; 3: 416-421.
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