Pharmacokinetics of Intravenous Isavuconazole in Solid Organ Transplant Recipients [Clinical Therapeutics]

Isavuconazole may be useful in treating and preventing fungal infections in solid organ transplant (SOT) recipients due to its safety profile and activity against Aspergillus and some Mucorales. Isavuconazole has favourable pharmacokinetics based on clinical trials in various patient populations, but data are limited in SOT recipients. We evaluated the steady state pharmacokinetics of Isavuconazole in 26 SOT recipients receiving the drug intravenously for prophylaxis. There was moderate inter-patient variability in isavuconazole pharmacokinetic parameters (coefficients of variation of 51% for area under the plasma concentration-time curve (AUC) and 59% for trough plasma concentration), which were in general less than previously reported for other mould-active azoles such as voriconazole and posaconazole. AUC and steady state trough plasma concentrations (C_trough) were significantly lower in women, patients with body mass index ≥18.5 kg/m², and those receiving hemodialysis. Trough plasma concentrations were highly-correlated with AUCs (R²=0.94), and can serve as suitable measure of isavuconazole exposure in patients. In conclusion, moderate inter-patient variability in isavuconazole exposure, identification of factors associated with lower exposure, recognition that C_trough is a surrogate marker for AUC and availability of a simple analytical method, suggest that therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least some SOT recipients. Future studies are needed to correlate isavuconazole exposure with patients' clinical outcomes, and to determine the clinical role of TDM.

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