Model based characterization of pharmacokinetic interaction between voriconazole and cytarabine in patients with acute myeloid leukemia

• Κύριος συγγραφέας: Ματθιός, Ανδρέας
• Άλλοι συγγραφείς: Σιβολαπένκο, Γρηγόριος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2014
• Θέματα: Voriconazole; Cytarabine; Acute myeloid leukemia; Pharmacokinetic interaction; Βορικοναζόλη; Κυταραβίνη; Οξεία μυελογενή λευχαιμία; Φαρμακοκινητική αλληλεπίδραση; 615.704 5

Voriconazole is a broad spectrum antifungal agent. Patients with acute myeloid leukemia that are susceptible to fungal infections receive simultaneously voriconazole and antitumor regimens. Drug-drug interactions between voriconazole and cytarabine involving the CYP3A4 enzyme are thought to affect the pharmacokinetic profile of the drugs and as a result their toxicological or pharmacological outcome. Population pharmacokinetic models were used to characterize these interactions and optimize the dose schemes after coadministration. Simulations and estimations were conducted by using NONMEM. The optimal dose for one hour intravenous infusion of voriconazole was estimated to 5mg/h. The proposed time points based on the pharmacokinetic profile of voriconazole for validated the model by using a small cohort of patients are 2h, 26h, 27h, 50h, 51h, 120h, 335h, 336h after the first administration of the antifungal agent.