Voriconazole Prophylaxis Against Aspergillosis in Lung Transplant Recipients
A fixed dosage regimen of voriconazole is routinely used for prophylaxis of aspergillosis in lung transplant patients at our institution. We hypothesize that use of a fixed dosage voriconazole regimen leads to large degree of variability in drug exposure among lung transplant patients and consequently, therapeutic failures or toxicity. This is a three part study which will examine plasma and lung voriconazole concentrations achieved with the prophylactic regimen and assess for a correlation between these concentrations with efficacy and toxicity. We aim to conduct an initial pilot study in 12 lung transplant patients to characterize the pharmacokinetic profile of voriconazole with both intravenous and oral doses. The data gathered from the pilot pharmacokinetic study will then be utilized to correlate trough concentrations with total voriconazole drug exposure as measured by area under the plasma concentration versus time curve (AUC). Additionally, trough concentrations will be followed over nine weeks of the prophylactic treatment period in a larger cohort of patients to determine maintenance of consistency in trough concentrations and whether the plasma concentrations are predictive of efficacy and toxicity. Voriconazole lung concentrations will be measured in a pilot study of 12 patients who undergo a bronchoscopy procedure as part of their standard medical care in order to determine the relationship between plasma and lung concentrations. The information obtained from this three phase study will be utilized to characterize the pharmacokinetics of voriconazole in lung transplant patients. Further, it will be used to define an optimal therapeutic voriconazole regimen that will be individualized to target specific concentrations in the lung and plasma to maximize efficacy and minimize toxicity
Blood samples (5 mL) will be collected either from an existing indwelling intravenous catheter or via a catheter placed by a research nurse or phlebotomist. The samples will be centrifuged at 1,500 g for 10 minutes within 60 minutes of collection. The plasma will be separated into two separate cryovials and stored at - 80 C until the time of assay for Voriconazole.A standardized data collection sheet will be created by the study investigators and utilized to gather pertinent information on each study participant from the patient medical records and electronic databases. The type of information collected will include, but will not be limited to, demographic information, transplant history, periodic serum chemistry and hematology monitoring, medication regimen, plasma voriconazole level monitoring and efficacy and safety monitoring parameters.
Observational Model: Case-Only, Time Perspective: Prospective
Post Lung Transplantation
University of Pittsburgh Medical Center
University of Pittsburgh
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00177827
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
The transference of either one or both of the lungs from one human or animal to another.
Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.
Hematopoietic Stem Cell Transplantation
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.
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