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Voriconazole Plasma Concentration and Toxicity

12 Years
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Trial Information

Voriconazole Plasma Concentration and Toxicity

Voriconazole (Vfend(Registered Trademark), Pfizer) has achieved common usage at the NIH
(National Institutes of Health) Clinical Research Center for the treatment of fungal
infections in immunosuppressed patients. Toxicity includes relatively frequent but
reversible changes in vision and more infrequent, potentially serious hepatotoxicity,
decreased cognitive function and rash. Incidence of these more serious adverse events has
been difficult to ascertain because of the morbidity of underlying disease in patients
receiving voriconazole, but a minimum estimate is 10 percent. It is known that voriconazole
plasma concentrations vary between patients over a fifty-fold range but it is not known
whether toxicity is related to plasma drug exposure. The reason for the differing
voriconazole plasma concentrations between normal individuals is partly due to genetic
variations in hepatic cytochrome enzymes CYP2C9 and CYP2C19 (Cytochrome P450, family 2,
subfamily C, polypeptide 9 and 19, respectively). In patients with underlying illness, drug
interactions and decreased hepatic drug clearance may contribute to variability.

The purpose of the study is to record prospectively the adverse effects of voriconazole in
Clinical Center patients who have been prescribed the drug by their primary physician. We
will ask the primary physician to order a trough voriconazole plasma levels once a week. The
test will not be reported to the physician. Because interpretation of the test is unknown,
the physicians will be blinded to the report. Rather, the primary objective of the study is
to analyze the voriconazole plasma concentrations when the study is completed to determine
if there is a concentration and duration of drug exposure that correlates with toxicity. A
secondary objective is to determine the 2C9 and 2C19 genotype of patients and search for
possible correlations between genotype and plasma voriconazole concentrations.
Administration of other drugs given to the patient will be tracked to analyze whether any
previously unknown drug interactions seem to have changed the voriconazole plasma
concentration. The study will also determine the incidence of adverse effects of
voriconazole in our patient population.

Inclusion Criteria


Patients, at least 12 years old with no restriction of gender, race or disabilities,
followed by the National Institute of Allergy and Infectious Diseases (NIAID), National
Cancer Institute (NCI) and National Heart Lung and Blood Institute (NHLBI) who begin
treatment with voriconazole either oral or intravenous.

Patients who have a previous voriconazole course at least 7 days before current course.


Time elapsed greater than 15 days from initiation of voriconazole treatment for inpatients
and greater than 30 days from initiation of voriconazole treatment for outpatients.

Patients who the medical staffs caring for the patient not want entered into the study.

Patients unable to give informed consent, due to the severity of their medical condition
(Comatose patients, ICU patients under sedation).

Type of Study:


Study Design:



United States: Federal Government

Study ID:




Start Date:

January 2006

Completion Date:

June 2010

Related Keywords:

  • Pharmacology
  • CYP2C9
  • CYP2C19
  • Pharmacology
  • Genotype
  • Metabolism



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892