title: Effect of grapefruit juice and food on the pharmacokinetics of pirfenidone in healthy Chinese volunteers: a diet-drug interaction study.
abstract: 1. Ingestion of grapefruit juice and food could be factors affecting the pharmacokinetics of pirfenidone, a promising drug for treatment of idiopathic pulmonary fibrosis. 2. A randomized, open-label, three-period crossover study was carried out in 12 healthy Chinese male volunteers who were randomized to one of the three treatments: pirfenidone tablets (0.4 g) were orally administered to fasted or fed subjects, or with grapefruit juice. The washout period was 7 d. 3. Significantly reduced maximum plasma concentration (Cmax, 5.0 5 ± 1.39 versus 10.9 0 ± 2.94 mg·L(- 1)), modestly affected area-under-the-plasma concentration-time curve (AUC) from time zero to 12 h post dosing (AUC0-12 h, 21.8 9 ± 6.47 versus 26.1 6 ± 7.32 mg·h·L(- 1)) and delayed time to reach Cmax (Tmax) were observed in fed group compared with fasted group. Similar effects on Cmax (5.8 2 ± 1.23 versus 10.9 0 ± 2.94 mg·L(- 1)) and AUC0-12 h (modest but not statistically significant, 24.4 4 ± 7.40 versus 26.1 6 ± 7.32 mg·h·L(- 1)) were observed for grapefruit juice compared to fasted subjects. 4. Co-administration of pirfenidone with grapefruit juice resulted in modestly reduced overall oral absorption and significantly reduced peak concentrations compared to fasting, which was similar to effect of food ingestion. No adverse events were observed in the study, but relatively dramatic reduction of peak concentrations should raise concerns for clinical efficacy and safety.
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Jinqing
authors.initials: J
authors.lastname: Hu
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Dewei
authors.initials: D
authors.lastname: Shang
authors.affiliation: b Ebang Pharmaceutical Co. Ltd , Zhuhai , China , and.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Xu
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .|c Department of Pharmacy , Xinhui People's Hospital of Jiangmen , Jiangmen , China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: He
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Ni
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Zhanzhang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Chang
authors.initials: C
authors.lastname: Qiu
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Shuhua
authors.initials: S
authors.lastname: Deng
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Haoyang
authors.initials: H
authors.lastname: Lu
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhu
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Wencan
authors.initials: W
authors.lastname: Huang
authors.affiliation: a Institution of National Drug Clinical Trials, Guangzhou Brain Hospital (Guangzhou Huiai Hospital, the Affiliated Brain Hospital of Guangzhou Medical University) , Guangzhou , China .
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Wen
mesh_terms: D001628:Beverages; D032083:Citrus paradisi / Q000737:chemistry*; D003710:Demography; D004032:Diet; D005502:Food; D018565:Food-Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011728:Pyridones / Q000009:adverse effects / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D011728:Pyridones; C093844:pirfenidone
keywords: Diet–drug interactions; grapefruit juice; idiopathic pulmonary fibrosis; pharmacokinetics; pirfenidone