Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer
| Autor: | B. Melichar, T. Csõszi, I. Lang, Jun Suk Kim, B. Belanger, Jung Sub Kim, J. B. Gallego, Joon Oh Park, A. Cubillo, Kun-Ming Rau, Wen Wee Ma, Mark Wong, B. S. Adiwijaya, J. Fitzgerald, Jen-Shi Chen, I. Molnar |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Diarrhea Male medicine.medical_specialty Neutropenia Bilirubin Population Cmax Pharmacology Irinotecan 030226 pharmacology & pharmacy Gastroenterology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Internal medicine Neoplasms medicine Humans Pharmacology (medical) education Aged Body surface area education.field_of_study Clinical Trials as Topic business.industry Research Articles Middle Aged medicine.disease chemistry 030220 oncology & carcinogenesis Liposomes Liposomal Irinotecan Camptothecin Female business medicine.drug |
| Zdroj: | Clinical Pharmacology and Therapeutics |
| ISSN: | 1532-6535 0009-9236 |
| Popis: | Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2 ), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax ) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax . Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W. |
| Databáze: | OpenAIRE |
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