Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to <6 [intravenous (IV) only], 6 to <12, and 12 to <18 years), receiving 10 mg/kg (maximum 372 mg) isavuconazonium sulfate either IV or orally. A population PK model using weight-based allometric scaling was constructed with the pediatric IV and oral data plus IV data from a phase 1 study in adults. The best model was a 3-compartment model with combined zero-order and first-order input, with linear elimination. Stepwise covariate modeling was performed in Perl-speaks-NONMEM, version 4.7.0. None of the covariates examined, including age, sex, race, and body mass index, were statistically significant for any of the PK parameters. The area under the concentration–time curve at steady state (AUCSS) was predicted for pediatric patients using 1000 Monte Carlo simulations per age cohort for each administration route. The probability of target attainment (AUCSS range 60–233 μg·h/mL) was estimated; this target range was derived from plasma drug exposures in adults receiving the recommended clinical dose. Predicted plasma drug exposures were within the target range for >80% and >76% of simulated pediatric patients following IV or oral administration, respectively. IV and oral administration of isavuconazonium sulfate at the studied dosage of 10 mg/kg was well tolerated and resulted in exposure in pediatric patients similar to that in adults.

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