title: Single- and multiple-dose pharmacokinetics of pirfenidone, an antifibrotic agent, in healthy Chinese volunteers.
abstract: 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 (t(max) = 0.33-1 hours) and cleared (t((1/2)) = 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 (AUC(0-infinity) = 37.4 +/- 15.4 mg x h/L [fed] vs 46.6 +/- 16.8 mg x h/L [fasted]), rate of absorption was considerably (P < .001) prolonged (t(max) = 1.5 +/- 0.4 hours [fed] vs 0.7 +/- 0.2 hours [fasted]), and peak concentrations were significantly (P < .001) decreased (C(max) = 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.
authors: Department of Pharmacy of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Shanghai, China.
authors: Shaojun
authors: S
authors: Shi
authors: Jianhong
authors: J
authors: Wu
authors: Huating
authors: H
authors: Chen
authors: Hui
authors: H
authors: Chen
authors: Jun
authors: J
authors: Wu
authors: Fandian
authors: F
authors: Zeng
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002681:China; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D011658:Pulmonary Fibrosis / Q000188:drug therapy; D011728:Pyridones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012737:Sex Factors
chemical_list: D011728:Pyridones; C093844:pirfenidone