Pharmacokinetics (PK) and Safety of Posaconazole (POS) as Prophylaxis for Invasive Fungal Infection (IFI) in High-Risk Patients (Pts).

A. LANGSTON1, A. J. ULLMANN 2, O. A. CORNELY 3, J. LIPTON 4, J. MAERTENS 5, D. WINSTON 6, J. PERFECT 7, P. CHANDRASEKAR 8, T. BRUNDAGE 9, D. ANGULO 9, H. PATINO 9, G. KRISHNA 9;

Author address: 

1Emory Univ. Hosp., Atlanta, GA, 2J. Gutenberg Univ., Mainz, Germany, 3Univ. Koeln, Koeln, Germany, 4Princess Margaret Hosp., Toronto, Canada, 5Univ. Hosp., Leuven, Belgium, 6UCLA CA, Los Angeles, CA, 7Duke Univ. Hosp., Durham, NC, 8Wayne State Univ.

Abstract: 

Background: POS PK and safety were analyzed in 2 trials (N~1200) of POS vs fluconazole [FLU] or itraconazole. Methods: 301 hematopoietic stem cell transplant (HSCT) recipients with graft-vs-host disease (GVHD) (study 1) and 304 neutropenic pts undergoing chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) (study 2) were randomized to receive POS 200 mg po tid. POS average and maximum plasma concentrations (Cav and Cmax) and safety were analyzed. Results: POS concentrations were available for 246 (study 1) and 215 (study 2) pts. Mean (SD) Cav and Cmax were 1122 (757) and 1499 (970) ng/mL (study 1) and 583 (381) and 685 (468) ng/mL (study 2). Cmax ranged from 0-4420 ng/mL (study 1) and from 92-2400 ng/mL (study 2). POS safety/tolerability was similar to that of FLU in both studies. Most common treatment-related adverse events (AEs) reported for POS (study 1, study 2) were nausea (7%, 7%), vomiting (4%, 5%), and diarrhea (3%, 7%). Bilirubinemia (3%, 2%) and hepatic enzyme increases (3%, 2%) were the most common hepatic treatment-related AEs. No association was observed between the incidence of these AEs and POS plasma concentration or between POS plasma concentration and either central nervous system events or visual disturbances. Mean Cav values were similar between pts with liver enzymes (at baseline in study 1; on or before day 7 in study 2) ≥ 2 x ULN and those with liver enzymes
2006

abstract No: 

A-1097

Full conference title: 

46th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 46th