Posaconazole Prophylaxis in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia: A Single Center Experience of Therapeutic Drug Monitoring

• Published in: Blood 2012-11, Vol.120 (21), p.2595-2595
• Main Authors: Pavan, Laura, Loregian, Arianna, Quinto, Angela Maria, Maggio, Speranza Antonia Di, Pagni, Silvana, Gazzola, Marco, De March, Elena, Palù, Giorgio, Semenzato, Gianpietro, Trentin, Livio, Vianello, Fabrizio, Zambello, Renato
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.2595.2595

Abstract 2595▪▪This icon denotes a clinically relevant abstract Posaconazole is indicated for prophylaxis and salvage therapy of invasive fungal infections. Based on pharmacokinetic-pharmacodynamic data, a minimum serum concentration higher than 0.5 mg/L and 1.0 mg/L has been proposed for prophylaxis and therapy, respectively. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. In fact only few reports correlate posaconazole plasma concentrations (PPCs) with breakthrough infection. In this retrospective single center study we evaluated the correlation of PPCs with breakthrough invasive mould infections (IMIs) in 50 patients with acute myeloid leukaemia (AML) who underwent chemoterapy (induction or salvage therapy) between July 2009 and March 2012. To measure the posaconazole concentration in human plasma, we developed and validated a rapid and simple high-performance liquid chromatography method. The method involved a solid-phase extraction of posaconazole using Oasis HLB cartridges, a reversed-phase liquid chromatography on an XTerra RP18 column with a mobile phase consisting of acetonitrile/ammonium acetate and ultraviolet detection. Patient characteristics and microbiological data such galactomannan detection and TDM were collected retrospectively. A total of 454 PPCs were measured before and 4 hours after administration in 50 patients with AML receiving posaconazole prophylaxis at dose of 200 mg 3 times/day. When plasma levels were below 0.5 mg/L, the dose was increased to 200 mg 4 times/day. Average levels below the target of 0.5 μg/mL were detected in 38 (76%) out of 50 cases; 5 out of 38 cases showed plasma concentrations