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03.08.2020 | Original Article

Excretion balance and pharmacokinetics following a single oral dose of [¹⁴C]-fedratinib in healthy subjects

verfasst von: Ken Ogasawara, Christine Xu, Vanaja Kanamaluru, Nicholas Siebers, Sekhar Surapaneni, Laurence Ridoux, Maria Palmisano, Gopal Krishna

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2020

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Abstract

Purpose

Fedratinib is an oral and selective kinase inhibitor with activity against wild type and mutationally activated Janus kinase 2 and FMS-like tyrosine kinase 3, for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis. This open-label mass balance study in healthy subjects investigated the excretion balance and systemic exposure of radioactivity after oral administration of [¹⁴C]-fedratinib; and the pharmacokinetics of fedratinib and its contribution to overall exposure of radioactivity.

Methods

Six healthy males received a single oral dose of 200 mg [¹⁴C]-fedratinib base (2.775 MBq, 75 μCi) as a solution. Blood, urine and feces samples were collected for up to 35 day postdose. Urine and feces samples were collected until the 24-h excretion of radioactivity fell below 0.5% of administered dose (at least 14 day postdose). Expired air was collected up to 8-h postdose. Total radioactivity (blood, plasma, urine, feces, and expired air) and fedratinib concentrations (plasma) were measured.

Results

Approximately 77% (23% unchanged) of fedratinib derived radioactivity was excreted in feces and 5% (3% unchanged) was excreted in urine. Excretion via expired air was negligible. The time to maximum concentration for both total radioactivity and parent drug was similar, with unchanged drug representing the majority of the circulating radioactivity. The ratio of blood to plasma concentration of radioactivity ranged from 0.615 to 0.753 indicating limited distribution of fedratinib and/or its metabolites into red blood cells.

Conclusions

Fedratinib derived radioactivity was primarily excreted in feces following a single oral dose of radiolabeled fedratinib to healthy subjects.

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Titel: Excretion balance and pharmacokinetics following a single oral dose of [14C]-fedratinib in healthy subjects
verfasst von: Ken Ogasawara
Christine Xu
Vanaja Kanamaluru
Nicholas Siebers
Sekhar Surapaneni
Laurence Ridoux
Maria Palmisano
Gopal Krishna
Publikationsdatum: 03.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2020
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04121-0

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Excretion balance and pharmacokinetics following a single oral dose of [¹⁴C]-fedratinib in healthy subjects