Evaluation of the effect of obesity on voriconazole serum concentrations

Abstract

Voriconazole is a second-generation triazole antifungal, approved by the FDA in 2002. Despite a decade of experience with voriconazole, there are limited published data analysing serum concentrations and toxicity in obese patients. Therefore, we evaluated voriconazole trough serum concentrations in obese and normal-weight patients in a retrospective cohort study. Voriconazole serum trough concentrations and toxicities were compared for obese (body mass index >35 kg/m(2)) versus normal-weight (body mass index 18.5-24.9 kg/m(2)) patients receiving 4 mg/kg voriconazole every 12 h. The obese group (n = 21) had significantly higher mean serum voriconazole trough concentrations than the normal-weight group (n = 66) (6.2 and 3.5 mg/L, respectively, P < 0.0001). Patients in the obese group also had higher rates of supratherapeutic voriconazole levels (>5.5 mg/L) than patients in the normal-weight group (67% versus 17%, respectively, P < 0.0001). However, hepatotoxicity and neurotoxicity rates did not differ between groups. The secondary endpoint compared mean serum voriconazole concentrations in the obese population when dosed at 4 mg/kg based on ideal body weight, adjusted body weight and actual body weight, which were statistically significantly different at 3.95, 3.3 and 6.2 mg/L, respectively (P = 0.0009). Therapeutic voriconazole concentrations (2.0-5.5 mg/L) occurred in 29% of obese patients when dosed on actual body weight, and 45% and 80% of patients when dosed on ideal body weight and adjusted body weight, respectively. Our results suggest a strong association between supratherapeutic concentrations and morbidly obese patients when dosed at 4 mg/kg actual body weight. Dosing voriconazole based on an ideal body weight or adjusted body weight may be appropriate for morbidly obese patients.