Rifampin decreases the plasma concentrations and effects of repaglinide

Objective: To study the effects of rifampin (INN, rifampicin) on the pharma cokinetics and pharmacodynamics of repaglinide, a new short-acting antidiab etic drug. Methods: In a randomized, two-phase crossover study, nine healthy volunteer s were given a 5-day pretreatment with 600 mg rifampin or matched placebo o nce daily On day 6 a single 0.5-mg dose of repaglinide was administered. Pl asma repaglinide and blood glucose concentrations were measured up to 7 hou rs. Results: Rifampin decreased the total area under the concentration-time cur ve of repaglinide by 57% (P < .001) and the peak plasma repaglinide concent ration by 41% (P = .001). The elimination half-life of repaglinide was shor tened from 1.5 to 1.1 hours (P < .01). The blood glucose decremental area u nder the concentration-time curve from 0 to 3 hours was reduced from 0.94 t o -0.23 mmol/L . h (P < .05), and the maximum decrease in blood glucose con centration from 1.6 to 1.0 mmol/L (P < .05) by rifampin. Conclusions: Rifampin considerably decreases the plasma concentrations of r epaglinide and also reduces its effects. This interaction is probably cause d by induction of the CYP3A4-mediated metabolism of repaglinide, It is prob able that the effects of repaglinide are decreased during treatment with ri fampin or other potent inducers of CYP3A4, such as carbamazepine, phenytoin , or St John's wort. (Clin Pharmacol Ther 2000;68:495-500.).