title: Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies.
abstract: Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.
authors.affiliation: Department of Pharmacy, West Virginia University Hospitals, Morgantown, West Virginia, USA Osborn Hematopoietic Malignancy and Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia, USA cumpstona@wvuhealthcare.com.
authors.forename: Aaron
authors.initials: A
authors.lastname: Cumpston
authors.affiliation: Department of Pharmacy, West Virginia University Hospitals, Morgantown, West Virginia, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Caddell
authors.affiliation: Department of Pharmacy, West Virginia University Hospitals, Morgantown, West Virginia, USA Osborn Hematopoietic Malignancy and Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Shillingburg
authors.affiliation: Department of Biostatistics, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biostatistics, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.affiliation: Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.affiliation: Osborn Hematopoietic Malignancy and Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Craig
authors.affiliation: Osborn Hematopoietic Malignancy and Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia, USA.
authors.forename: Abraham S
authors.initials: AS
authors.lastname: Kanate
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019072:Antibiotic Prophylaxis / Q000379:methods; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood* / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000097:blood* / Q000188:drug therapy*; D013535:Suspensions / Q000008:administration & dosage*; D013607:Tablets / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D013535:Suspensions; D013607:Tablets; D014230:Triazoles; C101425:posaconazole