The aim of the present study was to investigate the inhibitory effects of medroxyprogesterone acetate (MPA) on four important UGT isoforms (UGT1A1, 1A6, 1A9 and 2B7). 4-methylumbelliferone (4-MU) was used as a nonselective substrate, and recombinant UGT isoforms were utilized as an enzyme source. The results showed that MPA exhibited inhibitory effects on UGT2B7 (IC50 = 29.3 +/- 1.5 microM), with a negligible influence on other UGT isoforms. The results obtained from Lineweaver-Burk and Dixon plots showed that MPA competitively inhibited UGT2B7. The Ki value was calculated to be 7.2 microM. Based on the concentration of MPA in human liver, the magnitude of in vivo drug-drug interaction (DDI) was predicted. The [I]/Ki value was calculated to be 0.31, which suggested that DDIs might occur when MPA was co-administered with drugs which mainly undergo UGT2B7-mediated metabolism.