Evaluation of the effect of obesity on voriconazole serum concentrations.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
University of Michigan Hospitals and Health System, Pharmacy Services, Ann Arbor, MI 48109, USA.
Elizabeth
E
Koselke
Shawna
S
Kraft
Jeannina
J
Smith
Jerod
J
Nagel
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry*; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole