Open AccessPharmacokinetics and Safety of Oral Posaconazole in Neutropenic Stem Cell Transplant Recipients
Author(s) -
Paul O. Gubbins,
Gopal Krishna,
Angela Sansone-Parsons,
Scott Penzak,
Dong Li,
Monika Martinho,
Elias Anaissie
Publication year - 2006
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00157-06
Subject(s) - posaconazole , mucositis , pharmacokinetics , neutropenia , medicine , area under the curve , dosing , liter , hematopoietic stem cell transplantation , population , pharmacology , gastroenterology , absolute neutrophil count , transplantation , chemotherapy , itraconazole , antifungal , environmental health , dermatology
The pharmacokinetics of posaconazole oral suspension in neutropenic patients undergoing high-dose chemotherapy and stem cell transplantation were evaluated, and the association of plasma posaconazole exposure with the presence and severity of oral mucositis was explored in this nonrandomized, open-label, parallel-group, multiple-dose pharmacokinetic study. Thirty patients were enrolled and received one of three regimens (group I, 200 mg once daily; group II, 400 mg once daily; group III, 200 mg four times daily) for the duration of neutropenia. The mean total exposure for day 1, as shown by the area under the concentration-time curve from 0 to 24 h (AUC0-24 ), was 1.96 mg · h/liter in group I and was 51% higher in group II and in group III. Increases in AUC0-24 and maximum plasma concentration (C max ) in groups II and III were dose related. The AUC0-24 andC max values on day 1 were similar between groups II and III. There was interpatient variability of up to 68% in the pharmacokinetic values for our study population. Steady state was attained by days 5 to 6. Average steady-state plasma posaconazole trough values were 192, 219, and 414 ng/ml in groups I, II, and III, respectively. The AUC0-24 and apparent oral clearance increased by increasing dose and dosing frequency. Mucositis appeared to reduce exposure but did not significantly affect mean total posaconazole exposure (AUC andC max ) at steady state (P = 0.1483). Moreover, this reduction could be overcome by increasing the total dose and dosing frequency. Posaconazole was safe and well tolerated.