{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T08:46:48Z","timestamp":1782550008359,"version":"3.54.5"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PharmaMar S.A."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>This open-label, two-part, phase Ib drug\u2013drug interaction study investigated whether the pharmacokinetic (PK) and safety profiles of lurbinectedin (LRB), a marine-derived drug, are affected by co-administration of itraconazole (ITZ), a strong CYP3A4 inhibitor, in adult patients with advanced solid tumors. In Part A, three patients were sequentially assigned to Sequence 1 (LRB 0.8 mg\/m2, 1-h intravenous [IV] + ITZ 200 mg\/day oral in Cycle 1 [C1] and LRB alone 3.2 mg\/m2, 1 h, IV in Cycle 2 [C2]). In Part B, 11 patients were randomized (1:1) to receive either Sequence 1 (LRB at 0.9 mg\/m2 + ITZ in C1 and LRB alone in C2) or Sequence 2 (LRB alone in C1 and LRB + ITZ in C2). Eleven patients were evaluable for PK analysis: three in Part A and eight in Part B (four per sequence). The systemic total exposure of LRB increased with ITZ co-administration: 15% for Cmax, area under the curve (AUC) 2.4-fold for AUC0\u2013t and 2.7-fold for AUC0\u2013\u221e. Co-administration with ITZ produced statistically significant modifications in the unbound plasma LRB PK parameters. The LRB safety profile was consistent with the toxicities described in previous studies. Co-administration with multiple doses of ITZ significantly altered LRB systemic exposure. Hence, to avoid LRB overexposure when co-administered with strong CYP3A4 inhibitors, an LRB dose reduction proportional to CL reduction should be applied.<\/jats:p>","DOI":"10.3390\/md22040178","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T07:54:36Z","timestamp":1713340476000},"page":"178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetics and Safety of Lurbinectedin Administrated with Itraconazole in Cancer Patients: A Drug\u2013Drug Interaction Study"],"prefix":"10.3390","volume":"22","author":[{"given":"Irene","family":"Moreno","sequence":"first","affiliation":[{"name":"START Madrid\u2014Centro Integral Oncol\u00f3gico Clara Campal (CIOCC), Hospital Universitario HM Sanchinarro, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3459-871X","authenticated-orcid":false,"given":"Tatiana","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"START Madrid\u2014FJD, Hospital Universitario Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Calvo","sequence":"additional","affiliation":[{"name":"START Madrid\u2014Centro Integral Oncol\u00f3gico Clara Campal (CIOCC), Hospital Universitario HM Sanchinarro, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7320-6139","authenticated-orcid":false,"given":"Salvador","family":"Fudio","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Kahatt","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0391-4692","authenticated-orcid":false,"given":"Sara","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Luis","family":"Iglesias","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rom\u00e1n Octavio","family":"Calafati","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"P\u00e9rez-Ramos","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-8686","authenticated-orcid":false,"given":"Lola","family":"Montilla","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Zeaiter","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0550-8228","authenticated-orcid":false,"given":"Rubin","family":"Lubomirov","sequence":"additional","affiliation":[{"name":"PharmaMar S.A., 28770 Colmenar Viejo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1039\/b808331m","article-title":"Development of Yondelis (Trabectedin, ET-743). 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