Author:
Cojutti Piergiorgio,Candoni Anna,Simeone Erica,Franceschi Loretta,Fanin Renato,Pea Federico
Abstract
ABSTRACTThis study aimed to assess the influence of dose frequency and the presence or absence of cotreatment with proton pump inhibitors (PPIs) on the time to a target trough concentration (Cmin) of >700 ng/ml with posaconazole in the first 8 days of antifungal prophylaxis in hematological patients. This was a retrospective, observational study performed with 42 adult patients with acute myeloid leukemia who underwent posaconazole prophylaxis with 200 mg every 8 h (q8h) or 200 mg q6h after receiving induction chemotherapy and who had at least three subsequent therapeutic drug monitoring assessments during the first 8 days of treatment. The cohort was split into four groups (group 1, 200 mg q8h without PPI; group 2, 200 mg q8h with PPI; group 3, 200 mg q6h without PPI; group 4, 200 mg q6h with PPI). Rapid attainment of the targetCminwas obtained only in group 3 (P< 0.01) (medianCminon day 4 of 935.5 ng/ml [interquartile range, 760.0 to 1,270.0 ng/ml] in group 3, versus 567.0 ng/ml [346 to 906 ng/ml] in group 1, 420.0 ng/ml [326.2 to 527.2 ng/ml] in group 2, and 514.0 ng/ml [403.7 to 564.7 ng/ml] in group 4). A linear accumulation of posaconazole over time was observed among patients in groups 1 and 3, regardless of the total daily dosage, differently from what occurred among those receiving PPI cotreatment (groups 2 and 4). Dose intensification (200 mg q6h) coupled with avoidance of PPI coadministration may represent a very powerful strategy to rapidly achieve effective concentrations with posaconazole in neutropenic hematological patients.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
22 articles.
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