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Voriconazole trough levels are higher in males and in older patients

May 05 2020

The target range for voriconazole trough levels is approximately between 2 and 5.5 mcg/ml for treatment, or 1 and 4 mcg/ml for prophylaxis. Levels below this may be less effective, while levels above this are associated with toxicity. However, achieving this in practice can be tricky because many factors are known to affect serum concentrations, for example creatinine clearance, liver cirrhosis, drug interactions and genetic polymorphisms in cytochrome P450 (CYP) genes, especially CYP2C19.

Dr Sarah Allegra and colleagues in Italy looked at 330 hospital patients receiving voriconazole (150 IV, 180 oral) for treatment of fungal infection. Median dosages were 7.9 mg/kg for IV route (IQR 5.9-9.3), or 400mg for oral route (IQR 400-600 mg). Trough concentrations were measured by HPLC after 5 days (i.e. during steady state).

Trough levels were highly variable between patients, and both age and sex had an effect. While 33% of males had subtherapeutic levels (<1mcg/ml), the proportion was 48% for females. The authors speculate that this could be caused by differences in body fat percentage or in how sex hormones affect drug metabolism. Older age was also associated with higher levels, perhaps due to reduced clearance in older age.