Effect of rifampicin on the pharmacokinetics of pioglitazone

Results Rifampicin decreased the mean total area under the plasma concentration-time curve (AUC 0 −∞ ) of pioglitazone by 54% (range 20–66%; P = 0.0007; 95% confidence interval − 78 to − 30%) and shortened its dominant elimination half-life ( t 1/2 ) from 4.9 to 2.3 h ( P = 0.0002). No significant effect on peak concentration ( C max ) or time to peak ( t max ) was observed. Rifampicin increased the apparent formation rate of MIV and shortened its t max ( P < 0.01). It also decreased the AUC 0 −∞ of M-IV (by 34%; P = 0.0055) and M-III (by 39%; P = 0.0026), shortened their t 1/2 (M-IV by 50%; P = 0.0008, and M-III by 55%; P = 0.0016) and increased the AUC 0 −∞ ratios of M-IV and M-III to pioglitazone by 44% ( P = 0.0011) and 32% ( P = 0.0027), respectively. Rifampicin increased the M-IV/pioglitazone and M-I II/pioglitazone ratios in urine by 98% ( P = 0.0015) and 95% ( P = 0.0024). A previously unrecognized metabolite MXI, tentatively identified as a dihydroxy metabolite, was detected in urine during both phases, and rifampicin increased the ratio of M-XI to pioglitazone by 240% ( P = 0.0020).

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