Bioavailability of Voriconazole

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to obtain the absolute bioavailability of voriconazole in critically ill ICU patients, because pharmacokinetics can be different in critically ill patients due to alterations in function of various organs and body systems compared with healthy volunteers.

Detailed Description
-----------------
The bioavailability of voriconazole, based on healthy volunteers, is estimated to be >90%. Due to the high bioavailability of voriconazole, switching between oral and intravenous administration is permitted if clinically allowed. Few data are available for the bioavailability of voriconazole in critically ill patients. However, to obtain a therapeutic concentration of voriconazole (>1.5 mg/L, which is associated with a beneficial response to treatment) one study showed that a higher oral dose is required compared with the intravenous dose, to obtain this therapeutic concentration. Therefore, the pharmacokinetics can be changed in critically ill patients, including bioavailability. In this study, patients who receive voriconazole orally (prescribed by their attending physician) will receive one intravenous dose of voriconazole instead of the oral dose. The intravenous dose will be the same as the oral dose voriconazole.

Official Title
-----------------
Bioavailability of Voriconazole in Critically Ill Patients

Conditions
-----------------
Voriconazole, Bioavailability, Critically Ill

Intervention / Treatment
-----------------
* Other: Dosage form of voriconazole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged ≥ 18 yrs; Treatment with voriconazole; Admission to an ICU; Written informed consent. Exclusion Criteria: Blood sampling by central venous catheter or peripheral cannula not possible; Concomitantly using a strong inhibitor or inducer of cytochrome P450.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Bioavailability<br>1 arm, different dosage form | Other: Dosage form of voriconazole<br>* Instead of an oral dose of voriconazole, patients receive one intravenous dose of voriconazole (in the same dose as the oral dose).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The bioavailability of voriconazole in critically ill patients | Bioavailability will be determined by comparing the area under the concentration time curve (AUC) of an intravenous and oral dose of voriconazole. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of bioavailability of voriconazole with disease severity | Disease severity will be determined using the APACHE IV score | 1 day | 
| Correlation of bioavailability of voriconazole with the degree of inflammation | To determine the degree of inflammation C-reactive protein (CRP) will be determined | 1 day |