Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 3:21 AM
Ignite Modification Date:
2025-12-25 @ 3:21 AM
NCT ID:
NCT00371605
Brief Summary:
A fixed-dosing regimen of voriconazole is routinely used as prophylaxis against aspergillosis in liver transplant patients admitted to the transplant intensive care unit at UPMC. We hypothesize that use of a fixed-dosing regimen of voriconazole will lead to a large degree of variability in drug exposure among liver transplant patients due to: 1) variability in absorption and elimination caused by physiological characteristics unique to this patient population 2) its non-linear pharmacokinetics and 3) the potential for polymorphism in the genes that encode for cytochrome P-450 enzymes that metabolize voriconazole. This is a pilot clinical pharmacokinetic evaluation that will: 1) characterize the plasma concentration versus time profile of voriconazole in liver transplant patients receiving a fixed-dosing regimen to assess for extremes in systemic exposure 2) determine the oral bioavailability of voriconazole in liver transplant patients 3) assess for functionally significant allelic variation of the cytochrome P-450 enzymes that metabolize voriconazole (CYP2C9, CYP2C19 and CYP3A4/5) in both recipient blood and allograft tissue that may contribute extremes in systemic exposure among liver transplant patients. This evaluation will allow for an assessment of the adequacy of the prophylactic regimen in achieving therapeutic drug concentrations in all subjects. Additionally, the utility of genotyping as a clinical tool to identify patients at risk for extremes in voriconazole exposure will be evaluated. The characterization of the pharmacokinetics in liver transplant patients may be utilized to define an optimal therapeutic regimen that will be individualized to target specific concentrations to maximize efficacy and minimize side-effects.
Detailed Description:
All liver transplant patients receiving voriconazole prophylaxis are eligible to participate in this study. We propose a single-center, observational study in 15 liver transplant patients who are admitted to the ICU and receiving voriconazole prophylaxis as part of standard care. Each patient will undergo blood sampling (27 mL) on one occasion (Pharmacokinetic Study I), while receiving oral voriconazole. A small portion of blood (1 mL) collected during this blood sampling period will be retained for genotyping (specific aim III).
Voriconazole prophylaxis is most often administered to liver transplant patients via the oral route (200 mg twice daily). However, circumstances may arise necessitating the administration of intravenous doses of voriconazole for a subset of patients, as part of their standard care. . Thus, these patients will undergo blood sampling on a maximum two additional occasions: 1) surrounding an intravenous dose dose (27 mL) 2) surrounding an oral dose (27 mL) .
The amount of voriconazole present in the blood samples will be measured via high pressure liquid chromatography. Individual plasma concentration time profiles will be determined following oral and intravenous dosing, respectively. Pharmacokinetic parameter estimates will be derived via population and individual pharmacokinetic data analysis.
The use, dose, and frequency of the medication voriconazole is up to the clinical staff. We will not be altering the delivery, dose or use of the drug. Therefore we cannot provide you with the requested information because it will all depend on the clinical team. We are not intervening to enroll subjects. Subjects will only be enrolled if they are placed on voriconazole and they agreed to participate.
Study:
NCT00371605
Study Brief:
Protocol Section:
NCT00371605