Voriconazole: A Review of Population Pharmacokinetic Analyses

Numerous population pharmacokinetic studies on voriconazole have been conducted in recent years. This review aimed to comprehensively summarize the population pharmacokinetic models for voriconazole and to determine which covariates have been identified and which remain to be explored. We searched the PubMed and EMBASE databases from inception to March 2018 for population pharmacokinetic analyses of voriconazole using the nonlinear mixed-effect method. A total of 16 studies were included in this review, of which 11 models were described in adult populations, four were described in pediatric populations, and the remaining study included both adult and pediatric populations. The absorption profiles of voriconazole in both adult and pediatric studies were best described as first-order absorption models. The typical distribution volumes were similar in adult and pediatric patients, but the estimated clearances in pediatric patients were significantly higher than those in adult patients. The most commonly identified covariates were body weight, the cytochrome P450 2C19 genotype, liver function, and concomitant medications. Only one study evaluated the model using an external method. Further population pharmacokinetic studies on pediatric patients aged younger than 2 years are warranted. Furthermore, new or controversial potential covariates, such as inflammation, the cytochrome P450 3A4 genotype, concomitant medications (particularly various types and dosages of proton pump inhibitors and glucocorticoids), and various measures of body weight, should be tested because the unexplained variability remains relatively high. In addition, previously published models should be externally evaluated, and the predictive performance of the various models should be compared.