A phase I study of fluzoparib tablet formulation, an oral PARP inhibitor: effect of food on the pharmacokinetics and metabolism after oral dosing in healthy Chinese volunteers.

OBJECTIVE

To evaluate the effect of food on the pharmacokinetics (PK) of fluzoparib capsule.

METHODS

PK data were obtained after fluzoparib treatment in a crossover design study. Single-dose fluzoparib (120 mg) was administered under fasted and fed conditions to 16 healthy subjects. Metabolism and transformation fluzoparib were analyzed by liquid chromatograph-tandem mass spectrometry in the first period. Safety was also assessed.

RESULTS

The absorption rate of fluzoparib was slower in the fed group (t delayed by 3 h), and peak exposure (C) of fluzoparib in plasma decreased by 19.8% ( < 0.05) compared with the fasted group. The area under the curve (AUC) of fluzoparib was not statistically different between the fasted and fed conditions. The 90% confidence intervals for the C and AUC were 69.77-92.24% and 84.88-102.26%, respectively. Five, seven, and five fluzoparib metabolites were isolated from plasma, urine, and feces samples, respectively. Most treatment-emergent adverse events were grade I or II.

CONCLUSIONS

The presence of food decreased the absorption rate and peak exposure time of fluzoparib; however, the AUC did not significantly change compared with the fasted condition. Therefore, oral administration does not alter the efficacy and safety profile of fluzoparib.