{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:46:10Z","timestamp":1790934370870,"version":"4.1.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the penetration of olorofim, a novel antifungal agent into the tissues of the rat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Quantitative whole-body autoradiography was used to assess the distribution and tissue penetration in male and female rats following a single 2-hour IV infusion of [14C]-olorofim.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Radioactivity was rapidly and extensively distributed throughout many tissues in both sexes with maximal concentrations observed soon after start of the infusion. Thereafter radioactivity declined and at 336\u2005h (final timepoint), concentrations of radioactivity in most tissues were below the limit of quantification. The pattern of radioactive distribution was similar at all timepoints with concentrations greatest in liver, kidney cortex, adrenal cortex, abdominal and brown fat; the lowest concentrations were observed in the whole eye and at the bone surface (with levels similar to plasma in bone marrow and uveal tract\/retina). Tissue:plasma radioactivity concentration ratios for most tissues were above unity during the period 2.25 to 72\u2005h post-start of infusion. Radioactivity was detected in tissues frequently reported as sites of systemic fungal infections such as the lung, brain, kidney, bone and eye. Pharmacokinetic analyses showed that at early timepoints &amp;gt;75% of circulating radiolabelled material was intact olorofim confirming that olorofim is present in these key tissues at levels similar to or exceeding those seen in plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Olorofim distributes widely into rat tissues including those frequently infected by fungi, indicating its potential to treat systemic fungal infections caused by susceptible species, a finding in agreement with recent clinical reporting from a Phase 2 trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag120","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T12:38:30Z","timestamp":1773751110000},"source":"Crossref","is-referenced-by-count":3,"title":["The tissue distribution and pharmacokinetics of [14C]-olorofim following intravenous dosing in the rat"],"prefix":"10.1093","volume":"81","author":[{"given":"Derek","family":"Law","sequence":"first","affiliation":[{"name":"F2G Ltd , Alderley Park, Macclesfield SK10 4TF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ayrton","sequence":"additional","affiliation":[{"name":"F2G Consultant , Hertfordshire ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Kennedy","sequence":"additional","affiliation":[{"name":"F2G Ltd , Alderley Park, Macclesfield SK10 4TF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"F2G Ltd , Alderley Park, Macclesfield SK10 4TF 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