Serial Plasma Voriconazole Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation

Plasma voriconazole concentrations vary considerably between patients receiving standard dosing, and trough voriconazole concentrations are known to affect efficacy and toxicity. Temporal variations in serial plasma voriconazole concentrations through the course of therapy in hematopoietic stem cell transplantation patients has not been carefully described. Paired voriconazole concentrations in 64 patients were studied to determine the predictability of the second concentration based on the first. The difference between the two values was <5% in six patients. In 25 patients, the second concentration was higher by a median of 40%. In 33 patients, the subsequent concentration was lower by a median of 59%. For patients with an initial concentration of <2 mu g/ml, the correlation between the two values was poor (r = 0.24; P < 0.17). For those with an initial concentration of >= 2 mu g/ml, the correlation was good (r = 0.72; P < 0.0001). There was no relationship between the magnitude of the change and the time elapsing between the two measurements. Among the 43 patients who had an initial concentration of >= 1 mu g/ml, the two voriconazole measurements were strongly correlated (r = 0.66, P < 0.0001), but only 67% had a voriconazole serum concentration of >= 1 mu g/ml on the second measurement. No studied variables were reliable predictors in identifying concentrations above or below 1 or 2 mu g/ml. Our data suggest that variations in voriconazole concentrations are unpredictable despite standard dosing, and the acceptability of a concentration on one occasion cannot be extrapolated to future concentrations in the same patient. This suggests that ongoing therapeutic drug monitoring and dose adjustment may be beneficial in patients requiring prolonged voriconazole therapy.