Pharmacokinetic/pharmacodynamic analysis of voriconazole against Candida spp. and Aspergillus spp. in allogeneic stem cell transplant recipients.

Pharmacokinetic/pharmacodynamic analysis of voriconazole against Candida spp. and Aspergillus spp. in allogeneic stem cell transplant recipients.

Ther Drug Monit. 2019 May 23;:

Authors: Perez-Pitarch A, Guglieri-Lopez B, Ferriols-Lisart R, Pérez A, Ezquer-Garín C, Hernández-Boluda JC, Piñana JL, Navarro D, Solano C, Alós-Almiñana M

Abstract
OBJECTIVE: To evaluate the adequacy of different dosing regimens of voriconazole for the prophylaxis of invasive candidiasis and aspergillosis in adult allogeneic stem cell transplant recipients (ASCTRs) by means of population pharmacokinetic (PK) modelling and simulation.
METHODS: ASCTRs receiving voriconazole were included in this observational study. A population PK model was developed. Three oral voriconazole dosing regimens were simulated: 200, 300 and 400 mg BID. The pharmacodynamic target was defined as fAUC0-24/MIC ≥ 24.7. A probability of target attainment (PTA) ≥90% was considered optimal. The cumulative fraction of response (CFR) was defined as the fraction of patients achieving the pharmacodynamic target when a population of simulated patients is matched with a simulated population of different Candida spp. and Aspergillus spp. The percentage of patients with trough plasma concentrations at steady state (Ctrough) within the reference range (1-5.5 mg/L) was also calculated.
RESULTS: A two-compartment PK model was developed using data from 40 patients, which contributed 237 voriconazole plasma samples, including trough and maximum concentrations. Voriconazole 200, 300, and 400 mg BID achieved PTA ≥90% for MIC values ≤0.25 mg/L, ≤0.38 mg/L, and ≤0.50 mg/L, respectively. The CFR for A. niger, A. versicolor, and A. flavus increased >10% when increasing voriconazole dose from 200 to 400 mg BID (from 72.5 to 89.5% for A. niger; from 77.7 to 88.7% for A. versicolor; and from 82.4 to 94.9 % for A flavus). The percentage of patients with Ctrough within the reference range increased 15% when voriconazole dose was increased from 200 to 300 mg BID.
CONCLUSION: The pharmacokinetic simulations in this study suggest that transplant recipients on voriconazole prophylaxis against invasive candidiasis or aspergillosis are likely to achieve the target concentrations associated with the desired treatment outcomes if the maintenance dose is 200 mg BID. However, Aspergillus spp. with high MICs could require higher maintenance doses.

PMID: 31136417 [PubMed – as supplied by publisher]

Source: Industry