Voriconazole trough may be linked to survival in children

A pharmacokinetic association may exist between a voriconazole trough >1,000 ng/mL and survival in children, particularly after enteral dosing, according to results of a recent study.

The results also indicate a link between a trough >1,000 ng/mL and marked pharmacokinetic variability. The researchers wrote that these results may justify the measurement of serum concentrations.

Records were reviewed for 207 serum voriconazole concentration measurements taken among 46 children who had had ≥1 measurement. The age range of patients was 0.8 to 20.5 years. The study duration was May 1, 2006 to June 1, 2007.

Results indicated that a two-compartment Michaelis-Menten pharmacokinetic model most closely fit the data, but that that model explained only 80% of the observed variability.

A 2.6-fold increase in the OR for death was observed for each trough serum voriconazole concentration <1,000 ng/mL (95% CI, 1.6-4.8). Data from a statistical simulation indicated that an IV dose of 7 mg/kg or an oral dose of 200 mg twice daily could achieve a trough>1,000 ng/mL in most patients, but with a wide range of possible concentrations.

The researchers observed a 28% crude mortality rate.

There was no association between serum voriconazole concentration and hepatotoxicity.

Neely M et al. Clin Infect Dis. 2009;50:27-36.