Bioavailability of Voriconazole

Overview

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.

Full Title of Study: “Bioavailability of Voriconazole in Critically Ill Patients”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
• Study Primary Completion Date: June 2016

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.

Interventions

• Other: Dosage form of voriconazole
  • Instead of an oral dose of voriconazole, patients receive one intravenous dose of voriconazole (in the same dose as the oral dose).

Arms, Groups and Cohorts

• Other: Bioavailability
  • 1 arm, different dosage form

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • University Medical Center Groningen
• Provider of Information About this Clinical Study
  • Principal Investigator: JWC Alffenaar, PharmD, PhD – University Medical Center Groningen
• Overall Official(s)
  • Jan-Willem Alffenaar, PharmD, PhD, Principal Investigator, University Medical Center Groningen