Objective: To study the effects of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of repaglinide, a new short-acting antidiabetic drug.
Methods: In a randomized, two-phase crossover study, nine healthy volunteers were given a 5-day pretreatment with 600 mg rifampin or matched placebo once daily. On day 6 a single 0.5-mg dose of repaglinide was administered. Plasma repaglinide and blood glucose concentrations were measured up to 7 hours.
Results: Rifampin decreased the total area under the concentration-time curve of repaglinide by 57% (P < .001) and the peak plasma repaglinide concentration by 41% (P = .001). The elimination half-life of repaglinide was shortened from 1.5 to 1.1 hours (P < .01). The blood glucose decremental area under the concentration-time curve from 0 to 3 hours was reduced from 0.94 to -0.23 mmol/L x h (P < .05), and the maximum decrease in blood glucose concentration from 1.6 to 1.0 mmol/L (P < .05) by rifampin.
Conclusions: Rifampin considerably decreases the plasma concentrations of repaglinide and also reduces its effects. This interaction is probably caused by induction of the CYP3A4-mediated metabolism of repaglinide. It is probable that the effects of repaglinide are decreased during treatment with rifampin or other potent inducers of CYP3A4, such as carbamazepine, phenytoin, or St John's wort.