Effect of Food on the Pharmacokinetics of Pirfenidone Capsules in Healthy Volunteers / 中国药师

ABSTRACT

Objective: To compare the pharmacokinetics and bioavailability of pirfenidone in the fasted and fed states in healthy volunteers. Methods: An open-label, randomized crossover study was conducted in 12 healthy subjects. Food effects were examined by comparing pharmacokinetic data of pirfenidone after administration of a single oral 400 mg dose under fasted or fed conditions. Plas-ma pirfenidone concentration was determined by an HPLC method and its pharmacokinetic parameters were calculated with DAS v2. 0 software. Results: Under fasted and fed conditions, the concentration-time profiles of pirfenidone were fitted a one-compartment model and the pharmacokinetic parameters were as follows t1/2were (2. 16 ± 0. 47) and (2. 05 ± 0. 42) h;tmaxwere(0. 69 ± 0. 16)and (1. 46 ± 0. 40)h;Cmaxwere (12. 95 ± 1. 79) and (9. 16 ± 2. 87) mg·L-1;AUC0-12were (44. 97 ± 15. 06) and (36. 19 ± 14. 44) mg·h·L-1;AUC0-∞were (46. 55 ± 16. 79) and (37. 41 ± 15. 43) mg·h·L-1, respectively. When compared with that of the fasted group, tmaxwas significantly increased (P<0. 001) while Cmaxand AUC were remarkedly decreased in the fed group (P<0. 001 and P<0. 01, respectively). Conclusion: Concomitant food intake significantly influences the pharmacokinetics and bioavail-ability of pirfenidone as indicated by reducing its extent and rate of absorption, which is associated with better tolerability.