J Clin Pharmacol
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PHARMACOKINETICS

Single- and Multiple-Dose Pharmacokinetics of Pirfenidone, an Antifibrotic Agent, in Healthy Chinese Volunteers

Shaojun Shi, MD, Jianhong Wu, MD, Huating Chen, BS, Hui Chen, MS, Jun Wu, MD and Fandian Zeng, MD

From the Department of Pharmacy of Union Hospital (Dr Shi, Dr Huating Chen) and the Institute of Clinical Pharmacology (Dr Jianhong Wu, Dr Hui Chen, Dr Zeng), Tongji Medical College, Huazhong University of Science and Technology, and Shanghai Genomics Inc, Shanghai, People's Republic of China (Dr Wu).

A randomized, dose-escalating study evaluated the pharmacokinetics of single and multiple oral doses of pirfenidone, a promising antifibrotic agent, in 48 healthy Chinese volunteers. The effects of sex and food on the pharmacokinetics of pirfenidone were also evaluated. Pharmacokinetics was determined from serial blood samples obtained up to 12 hours after administration of single 200-, 400-, or 600-mg doses of pirfenidone and after multiple doses of 400 mg administrated 3 times daily (tid). Plasma levels of pirfenidone and areas under the curve were found to be proportional to dose. Pirfenidone was rapidly absorbed (tmax = 0.33-1 hours) and cleared (t1/2 = 2-2.5 hours). Pharmacokinetic parameters after multiple doses were similar to those after single doses. Food had a significant effect (P < .01) on the extent of absorption (AUC0-{infty} = 37.4 ± 15.4 mg·h/L [fed] vs 46.6 ± 16.8 mg·h/L [fasted]), rate of absorption was considerably (P < .001) prolonged (tmax = 1.5 ± 0.4 hours [fed] vs 0.7 ± 0.2 hours [fasted]), and peak concentrations were significantly (P < .001) decreased (Cmax = 9.2 ± 2.9 mg/L [fed] vs 13.0 ± 1.8 mg/L [fasted]). No significant sex differences were noted for pharmacokinetic variables. Pirfenidone was well tolerated. These results support a tid regimen of pirfenidone for the management of idiopathic pulmonary fibrosis. Concomitant intake of food will reduce the rate and extent (about 20%) of absorption, which is associated with better tolerability of pirfenidone.

Key Words: Pirfenidone • antifibrotic agent • idiopathic pulmonary fibrosis • pharmacokinetics

Address for correspondence: Fandian Zeng, Institute of Clinical Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, Wuhan 430030, People's Republic of China;e-mail: fdzeng{at}163.com.


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