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

ABSTRACT

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_max delayed by 3 h), and peak exposure (C_max) of fluzoparib in plasma decreased by 19.8% (p < 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_max and AUC_0-∞ 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.

KEYWORDS:

• Poly(ADP-ribose) polymerase (PARP)
• fluzoparib
• pharmacokinetics
• food effect
• metabolism
• inhibitor
• phase I

Acknowledgments

The authors would like to thank the volunteers enrolled in this trial, as well as the staff who contributed to this trial.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

The authors are solely responsible for the design and conduct of this study. MW and YHD performed a review of the topic, and wrote and revised the manuscript. HZ took part in analyzing pharmacokinetics data. JXS and HC took part in the analysis and interpretation of data, and prepared all figures and tables. All the authors approved the final version of the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This project was financially sponsored by the following programs: National Major Scientific and Technological Special Project for Significant New Drug Development during the Thirteenth Five-Year Plan Period of China (Project No. 2017ZX09304004, 2017ZX09101001-002-004), the National Natural Science Foundation of China (Project No. 81602897).