| Autor: |
Moreno, Irene, Hernández, Tatiana, Calvo, Emiliano, Fudio, Salvador, Kahatt, Carmen, Martínez, Sara, Iglesias, Jorge Luis, Calafati, Román Octavio, Pérez-Ramos, Laura, Montilla, Lola, Zeaiter, Ali, Lubomirov, Rubin |
| Zdroj: |
Marine Drugs; Apr2024, Vol. 22 Issue 4, p178, 15p |
| Abstrakt: |
This open-label, two-part, phase Ib drug–drug 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–t and 2.7-fold for AUC0–∞. 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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