Pharmacokinetics of Voriconazole in Obese Subjects
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      Obese subjects may require a higher fixed oral maintenance dosing regimen of voriconazole
      compared to normal weight subjects to achieve comparable plasma exposures. The current study
      is designed to address this issue.
    

Detailed description: 
      The prevalence of obesity has increased tremendously in the past two decades. An estimated 1
      out of 5 persons in the United States are classified as obese. Under representation of obese
      patients in pharmacokinetic trials grossly limit generalizability of drug dosing
      recommendations in this emerging population. No published pharmacokinetic studies of
      voriconazole dosing in patients with obesity currently exist in the literature.
      Specifically,voriconazole pharmacokinetic data from subjects with a body mass index (BMI) ≥
      35 kg/m2(Class II and III obesity) are limited.

      Voriconazole is available as both an intravenous and oral formulation. Anecdotal experience
      suggest that the use of oral voriconazole to be significantly more prevalent that that of
      intravenous therapy. The current oral recommended dosing regimen for voriconazole includes
      use of 200 mg every 12 hours for patients who are over 40 kg. The dosage can be increased to
      300 mg by mouth every 12 hours in situations where a sufficient clinical response is not
      noted. A weight based dosing strategy is also utilized in patients with more serious
      infections (3-6 mg/kg IV Q 12 hours) such as invasive aspergillosis. Voriconazole
      demonstrates non-linear pharmacokinetics and so dosing based on total body weight may result
      in non-dose proportional exposure. For example, a 1.5 fold dose increment in voriconazole
      from 200 mg to 300 mg every 12 hours results in a 2.5 fold increase in exposure. The most
      appropriate body size descriptor is unknown (i.e. ideal body weight, fat free weight, lean
      body weight, etc.) for most antimicrobials, including voriconazole. As a consequence, the
      appropriateness of weight-based voriconazole dosage selection in obese patients is not known.
      Intuitively, weight based dosing (on total body weight) in this population could lead to
      higher than expected exposures (non-linear pharmacokinetics) and lead to potential adverse
      events. Therapeutic drug monitoring is increasingly advocated as a system to improve
      voriconazole dosing. However, an assay to measure voriconazole concentrations in the clinic
      is not routinely available. Hence, the current pilot study proposes to characterize the
      pharmacokinetic profile of voriconazole in obese subjects using two fixed dose regimens.
    

Intervention name(s): Voriconazole low dose; Voriconazole high dose
Intervention type(s): Drug; Drug
Intervention description(s): Voriconazole 400 mg po x 2 doses (loading dose)then 200 mg po twice daily x 7 doses; Voriconazole 400 mg po x 2 doses (loading dose)then 300 mg po twice daily x 7 doses
Other intervention name(s): Vfend; Vfend
Intervention MeSH terms: Voriconazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research
Keywords: Voriconazole; Pharmacokinetics; Obese; Healthy Volunteer