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Pharmacokinetic\u2010pharmacodynamic analyses were conducted to characterize the time course of absolute neutrophil count and platelet count recovery and to detect and quantify the effect of relevant covariates in patients with advanced solid tumors treated with lurbinectedin. Absolute neutrophil count, platelet count, and lurbinectedin total plasma concentration were assessed in 244 patients treated with lurbinectedin with varied dosing schedules and doses. A reference extended semimechanistic pharmacokinetic\u2010pharmacodynamic model of myelosuppression was used. Granulocyte colony\u2010stimulating factor (G\u2010CSF) administration was modeled as a dichotomous covariate, and platelet transfusions were included as a bolus dose into the last compartment of the model, representing the central circulation. Final models were suitable to describe the time course of absolute neutrophil count and platelet count recovery. A lurbinectedin dose of 3.2 mg\/m<jats:sup>2<\/jats:sup> every 3 weeks can be administered without primary prophylaxis with G\u2010CSF. G\u2010CSF followed by \u22642 dose reductions of 20%, if needed, gradually reduced grade 4 neutropenia from cycle 3 onward. BSA\u2010based dosing reduced the incidence of grade \u2265 3 thrombocytopenia. One\u2010week dose delays because of low absolute neutrophil count occurred in 3.5% of patients, thus supporting every\u20103\u2010week administration. CYP3A inhibitors produced absolute 11.0% and 6.2% increases in grade \u2265 3 neutropenia and thrombocytopenia, respectively. Neutropenia and thrombocytopenia after lurbinectedin administration to cancer patients are noncumulative, reversible, short lasting, and clinically manageable with secondary prophylaxis of G\u2010CSF or platelet transfusion and, if needed, dose reductions.<\/jats:p>","DOI":"10.1002\/jcph.1886","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T15:48:23Z","timestamp":1619711303000},"page":"1206-1219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Population Pharmacokinetic\u2010Pharmacodynamic Modeling and Covariate Analyses of Neutropenia and Thrombocytopenia in Patients With Solid Tumors Treated With Lurbinectedin"],"prefix":"10.1002","volume":"61","author":[{"given":"Carlos","family":"Fern\u00e1ndez\u2010Teruel","sequence":"first","affiliation":[{"name":"Pharma Mar  Madrid 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