Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects

Open Access
Publisher Website
Google Scholar
Abstract
Aims Our aim was to investigate the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide, a novel short‐acting antidiabetic drug. Methods In a randomized crossover study with two phases, 10 healthy volunteers took 600 mg rifampicin or placebo orally once daily for 5 days. On day 6 of both phases, they ingested a single 60 mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 7 h postdose. Results Rifampicin decreased the mean AUC(0,7 h) of nateglinide by 24% (range 5–53%; P = 0.0009) and shortened its half‐life (t1/2) from 1.6 to 1.3 h (P = 0.001). However, the peak plasma nateglinide concentration (Cmax) remained unchanged. The AUC(0,7 h) of the M7 metabolite of nateglinide was decreased by 19% (P = 0.002) and its t1/2 was shortened from 2.1 to 1.6 h by rifampicin (P = 0.008). Rifampicin had no significant effect on the blood glucose‐lowering effect of nateglinide. Conclusions Rifampicin modestly decreased the plasma concentrations of nateglinide probably by inducing its oxidative biotransformation. In some patients, rifampicin may reduce the blood glucose‐lowering effect of nateglinide.