Evaluation of posaconazole plasma concentrations achieved with the delayed‐release tablets in Korean high‐risk patients with haematologic malignancy

Abstract

Summary Background Posaconazole (PCZ) is a triazole approved for prophylaxis of invasive fungal infections. Objectives Herein, the impact of clinical variables on PCZ plasma concentrations (PPCs) attained with PCZ delayed‐release tablet (DRT) was investigated and compared with a historical cohort treated with PCZ oral suspension (OS). Patients/Methods Steady‐state PCZ PPCs in 513 patients with haematologic malignancy treated with PCZ‐DRT were assessed and impact of variables were analysed. Also, a comparison with matched historical cohort treated with PCZ‐OS was made. Results The median PPC in the PCZ‐DRT group was 1,308.9 ng/mL (range: 29.8‐10 455.9). Use of proton pump inhibitor (1181 vs 1344 ng/mL, P = .0337) in the AML/myelodysplastic syndrome remission induction group, diarrhoea (867 vs 1543 ng/mL, P = .0325) and gastrointestinal graft‐versus‐host disease (870 vs 1713 ng/mL, P = .0178) in the HSCT group were associated with lower PPCs. There was lack of evidence that hepatotoxicity was related with PCZ‐DRT. Higher prevalence of UGT1A4*3 allele (33.0%) was noted compared to allele frequency in Koreans in those with PPCs < 500 mg/mL. The median PPC in the PCZ‐DRT group was significantly higher than that in the PCZ‐OS group (1308.9 vs 713.0 ng/mL, P < .0001). Significantly less patients had PPCs < 700 ng/mL in the PCZ‐DRT group compared to the PCZ‐OS group (18.7% vs 48.0%, P < .0001). Conclusions Our study demonstrates that PCZ‐DRT has enhanced absorption and bioavailability than PCZ‐OS in real‐world clinical settings. In addition, specific factors associated with lower PPCs should prompt consideration of therapeutic drug monitoring in patients treated with PCZ‐DRT.

Antifungal Drugs TDM: Trends and Update

“…The major factors impacting PSZ exposure were high-fat meals, steroids, diarrhea, obesity, and hypoalbuminemia. 287,289,[291][292][293][294][295] PSZ DRT is significantly more bioavailable than the suspension, leading to better clinical outcomes for both prophylaxis and curative treatments. [296][297][298][299][300][301][302][303][304][305][306][307] Both formulations are not, therefore, interchangeable.…”