Voriconazole serum concentrations in obese and overweight immunocompromised patients: a retrospective review

Abstract

Study objective: To evaluate the relationship between voriconazole dose and corresponding serum concentrations in obese and overweight immunocompromised patients.

Design: Retrospective medical record review.

Setting: National Cancer Institute-designated comprehensive cancer center.

Patients: A total of 92 patients with hematologic malignancies and/or hematopoietic stem cell transplants who received voriconazole and had reported steady-state serum concentrations (peak, random, or trough) during 2005-2010; 124 serum concentrations were available for analysis.

Measurements and main results: Data on patient demographics, voriconazole concentrations, and other clinical and safety data were collected. Patients were stratified based on body mass index (BMI). Patients with higher BMIs tended to have significantly higher median random voriconazole concentrations with intravenous administration (6.4 mg/L for BMI ≥ 25 kg/m(2) vs 2.8 mg/L for BMI < 25 kg/m(2), p=0.04). This trend was more notable with the intravenous than the oral formulations. With the oral formulation, patients with a BMI of 25 kg/m(2) or greater had a median random concentration of 2.8 mg/L compared with 2.0 mg/L in patients with a BMI less than 25 kg/m(2) (p=0.18). Patients with a BMI of 25 kg/m(2) or greater also had a higher median daily voriconazole dose (640 vs 400 mg, p<0.001). No significant differences were noted in factors that would affect oral absorption of voriconazole (e.g., graft-versus-host disease) among BMI groups. When comparing all voriconazole concentrations, higher concentrations were associated with a greater percentage of patients who had alanine aminotransferase levels of more than 3 times the upper limit of normal. Patients with voriconazole random concentrations of 2 mg/L or greater had higher response rates (50%) than patients with concentrations lower than 2 mg/L (33%).

Conclusion: Standard voriconazole dosing using actual body weight in obese and overweight patients resulted in higher associated serum concentrations. Dosing using adjusted body weight may be necessary in this population in order to achieve optimal concentrations while preventing the potential for increased toxicity.