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Voriconazole, a new-generation azole, has broad antifungal activity. However, recent studies have suggested wide variability in plasma levels that could affect both efficacy and toxicity. Such differences are in part based on genetic polymorphisms in the cytochrome P450 metabolic system and on individual patient factors. To further explore this variability, investigators in Switzerland performed a population pharmacokinetic analysis among consecutive hospitalized adults who were receiving voriconazole for invasive fungal infections (N=55).
Plasma voriconazole concentrations rose linearly with increasing doses. Oral bioavailability was 63%. Significant decreases in clearance were seen in patients with grade 3 cholestasis. Sex, body weight, an…