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 (C_max, 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 (AUC_0–12 h, 21.8 9 ± 6.47 versus 26.1 6 ± 7.32 mg·h·L^{− 1}) and delayed time to reach C_max (T_max) were observed in fed group compared with fasted group. Similar effects on C_max (5.8 2 ± 1.23 versus 10.9 0 ± 2.94 mg·L^{− 1}) and AUC_0–12 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.

• Diet–drug interactions
• grapefruit juice
• idiopathic pulmonary fibrosis
• pharmacokinetics
• pirfenidone