Effect of food on the bioavailability and tolerability of the JAK2-selective inhibitor fedratinib (SAR302503): Results from two phase I studies in healthy volunteers.
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Zhang M, Xu C, Ma L, Shamiyeh E, Yin J, von Moltke LL, Smith WB
Effect of food on the bioavailability and tolerability of the JAK2-selective inhibitor fedratinib (SAR302503): Results from two phase I studies in healthy volunteers.
Clin Pharmacol Drug Dev. 2015 Jul;4(4):315-21. doi: 10.1002/cpdd.161. Epub 2014 Oct 27.
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- 27136912 [ View in PubMed]
- Abstract
Fedratinib (SAR302503/TG101348) is a Janus kinase 2 (JAK2)-selective inhibitor developed for treatment of patients with myelofibrosis. The effect of food intake on the pharmacokinetics (PKs) and tolerability of single-dose fedratinib was investigated in two Phase I studies (FED12258: 100 mg or 500 mg under fasted or fed [high-fat breakfast] conditions; ALI13451: 500 mg under fasted or fed [low- or high-fat breakfast] conditions) in healthy male subjects. At the 500 mg dose the fed:fasted ratio estimate for area under the plasma concentration-time curve extrapolated to infinity was 0.96 (100 mg; high-fat/fasted), 1.19-1.24 (500 mg; high-fat/fasted), and 1.22 (500 mg; low-fat/fasted). Fedratinib 500 mg attained peak plasma concentration 4 hours after a high-fat breakfast and 2-2.5 hours after a low-fat breakfast or under fasted conditions; terminal half-life was 76-88 hours (fasted) and 73-78 hours (fed). The most frequent adverse events were mild gastrointestinal toxicities, the incidence of which decreased following a high-fat breakfast compared with both fasted and low-fat breakfast conditions (17%, 67%, and 59% of subjects, respectively, in ALI13451). In conclusion, food intake had minimal impact on the PKs of fedratinib, and the tolerability of this drug was improved when taken following a high-fat breakfast.
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