CYCLOSPORINE PHARMACOKINETICS IN MARROW RECIPIENTS

The specific aims of this research application are to characterize the
pharmacokinetic disposition of Cyclosporine (CSP) and its major metabolites
in patients undergoing bone marrow transplantation for aplastic anemia or
hematologic malignancy. We plan to use a specific high-pressure liquid
chromatographic procedure developed in our laboratory to quantitate CSP.
Serial blood and urine samples will be collected to obtain a
pharmacokinetic profile for SCP and its major metabolites following oral
and intravenous administration. Concentration versus time data will be
fitted by computer to the appropriate pharmacokinetic mammilary model.
Half-lives, systemic and renal clearance, volume of distribution, and
absorption rate constant will be calculated with standard pharmacokinetic
equations. Cyclosporine concentrations after oral administration will be
compared to those after intravenous administration to calculate the
absolute bioavailability of the oral solution. Cyclosporine and CSP
metabolite concentrations will be correlated with concurrently collected
clinical data to determine the effects of hepatic and renal dysfunction,
oral nonabsorbable antibiotics, and acute graft-versus-host disease on CSP
or CSP metabolite pharmacokinetics. The results of this study may aid in
the design of rational CSP dosing regimens, defining optimal serum CSP
concentrations, and adjusting CSP dosage in the presence of organ
dysfunction or other clinical features.