{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:40:34Z","timestamp":1768455634512,"version":"3.49.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"New Medicine Clinical Research Fund","award":["524Z9141"],"award-info":[{"award-number":["524Z9141"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study investigated CYP3A4-mediated pharmacokinetic interactions between ruxolitinib (JAK1\/2 inhibitor for steroid-refractory acute and chronic graft-versus-host disease) and posaconazole (antifungal prophylaxis in haematological malignancies) to inform clinical dosing strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this open-label, fixed-sequence trial, eight Chinese patients with haematological malignancies received ruxolitinib 5 mg once daily (Day 1: monotherapy) followed by ruxolitinib 5 mg plus posaconazole 200 mg three times daily (Days 2\u20136: combination). Plasma concentrations of ruxolitinib and posaconazole were analysed using validated LC-MS\/MS. Geometric mean ratios (GMRs) with 90% CIs for PK parameters were calculated to assess PK interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All patients completed the study. Co-administration with posaconazole increased ruxolitinib AUC0\u201324h by 58% (GMR: 1.58; 90% CI: 1.32\u20131.88). Geometric mean AUC0\u201324h values were 179.80 \u03bcg\u00b7h\/L [monotherapy, coefficient of variation (CV) 39.26%] versus 283.60 \u03bcg\u00b7h\/L (combination, CV 41.42%). No significant change in Cmax was observed (GMR: 1.10; 90% CI: 0.90\u20131.36). Geometric mean of the maximum plasma concentration at steady state (Cmax,ss) and AUC0\u201324h of posaconazole were 1543.52 \u03bcg\/L (CV 41.81%) and 31\u200a404.37 \u03bcg\u00b7h\/L (CV 32.14%). There was no significant correlation between the systemic exposure of posaconazole (AUC or Cmax,ss) and the ratio of ruxolitinib AUC0\u201324h when co-administered versus administered alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although co-administration of posaconazole with ruxolitinib resulted in a statistically significant increase in ruxolitinib systemic exposure, the magnitude of this interaction was clinically moderate. Although ruxolitinib dose adjustment may not be routinely required when used concomitantly with posaconazole, close monitoring for ruxolitinib-related adverse effects is recommended under this combination therapy setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf398","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:10:40Z","timestamp":1760011840000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterizing CYP3A4-mediated drug interactions: a fixed-sequence pharmacokinetic Chinese study of posaconazole and ruxolitinib in haematological malignancies"],"prefix":"10.1093","volume":"81","author":[{"given":"Beibei","family":"Liang","sequence":"first","affiliation":[{"name":"Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of Chinese PLA General Hospital , 28 Fu Xing Road, Haidian District, Beijing 100853 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fifth Medical Center of Chinese PLA General Hospital , Beijing 100853 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songhua","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fifth Medical Center of Chinese PLA General Hospital , Beijing 100853 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of Chinese PLA General Hospital , 28 Fu Xing Road, Haidian District, Beijing 100853 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinru","family":"Zeng","sequence":"additional","affiliation":[{"name":"Center of Medicine 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