Aims: A phase I open-label study assessed the effect of multiple oral doses of a potent CYP3A4 inducer (rifampicin) on the pharmacokinetic profile of SHR2554, a novel enhancer of zeste homolog 2 inhibitor (EZH2) and CYP3A4 substrate. Methods: Eighteen adult Chinese healthy subjects were enrolled in this study. All participants received a single oral dose of SHR2554 (300 mg) on day 1, rifampin (600 mg) from day 4 to day 10 and day 12, the same dose was coadministered with SHR2554 (300 mg) and rifampicin (600 mg) on day 11. The primary endpoints were SHR2554 exposure parameters. Lack of drug–drug interaction was concluded if 90% confidence intervals (CIs) for the ratio of area under the plasma concentration–time curve (AUC) or maximum concentration (Cmax), with/without oral rifampicin, were within a pre-specified interval (0.80–1.25). Results: The Cmax, AUC0-t, and AUC0-∞ of administration alone and coadministration with rifampin were 177.265 ±127.9889 ng/mL, 17.001 ± 8.4759 ng/mL; 672.12 ± 507.390 h*ng/mL, 38.58 ± 19.495 h*ng/mL; and 721.50 ±514.386 h*ng/mL, 46.30 ± 20.750 h*ng/mL, respectively. Coadministration with rifampin decreased the least-squares geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ by 89%, 93%, and 93%, respectively. Well tolerance and acceptable safety profile showed during the trial. Conclusion: The exposure of SHR2554 was significantly decreased when coadministered with rifampicin. It is recommended to avoid concomitant use of SHR2554 and strong inducers of CYP3A4.

Aim: This study has been designed to assess the bioequivalence of the newly developed delayed-release oral tablets (test) 30 mg nifedipine compared to its marketed counterpart (30 mg; reference) in healthy adult Chinese volunteers. Methods: We conducted randomized, open-label, four-period, crossover trials, including a fasting trial and a fed trial. The subjects were administered the test or reference products in a 1:1 ratio at random throughout each period with 7 days washout period. Then, in the next session, they got the alternate products. Liquid chromatography-tandem mass spectrometry and WinNonlin software were used to evaluate the bioequivalence of nifedipine peak blood concentration (Cmax) and area under the concentration-time curve (AUC). Result: A total of 46 subjects participated in the fasting trial and 48 subjects in the postprandial trial. In both cases, the 90% CI of the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were in the equivalence range (80-125%). When nifedipine was given concomitantly with a high-fat meal, tmax was approximately twofold earlier, absorption was approximately 4.8% less, and Cmax changed little compared to fasting conditions. In addition, no serious adverse events were observed in the subjects. Conclusion: This study confirms the bioequivalence of the test and reference formulations of nifedipine extended-release tablets under fasting and postprandial conditions. Food giving leads to a much earlier Tmax, which is different from the results of other studies. The effect of food effect on the pharmacokinetics of nifedipine needs to be further explored.