The proposed project is aimed at populating and analyzing a large data repository from large academic institutions and reference laboratories to determine intra-individual pharmacokinetic variability and investigate pharmacokinetic-pharmacodynamic (PK-PD) relationships in an effort to characterize the therapeutic indices of commonly administered drugs. Specifically, this work will focus on the retrospective querying and anlaysis of data collected from individuals administered the immunosuppressant drug tacrolimus or those taking the anti-epileptic medication levetiracetam. An interdisciplinary team of clinical laboratory directors and clinical pathologists from a variety of laboratory settings will facilitate the establishment and population of the large data repository to meet the aforementioned goals. While the two goals of the project are somewhat independent, the information captured from both may be used synergistically to better characterize a drug's therapeutic index relative to its established within- individual pharmacokinetic variability. The two specific objectives of the proposed work include: 1) Characterization of within-individual pharmacokinetic variability for pilot study drugs, specifically the immunosuppressant drug tacrolimus and the anti-epileptic agent levetiracetam, using archived therapeutic drug monitoring data for individual patients, and 2) Establishment of a PK-PD relationship for the aforementioned pilot drugs using archived TDM data and concurrent clinical information for individual patients. The proposed work will be a close collaboration with other clinical laboratories performing therapeutic drug monitoring (TDM) including the Mayo Clinic (Drs. Paul Jannetto and Loralie Langman) and ARUP (Drs. Gwen McMillin and Kamisha Johnson-Davis).
Certain drugs vary widely in their blood concentration for patients taking the same dosage, and these drugs are managed using clinical laboratory testing. For these drugs, it is important to understand the optimal blood concentration range, within which the drug has the desired effect, but does not cause toxic effects for a patient. The proposed project will use existing laboratory data to investigate the variability of drug concentrations for individuals on one of two study drugs, and find the optimal blood concentration ranges based on clinical effects as determined the patient records. This can establish a model for future studies to find the best concentration range for various drugs.