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Biological membranes and other cellular barriers to drug transport yield the need for new and innovative delivery systems which enable the drug to reach the targeted site. In order for a drug to be efficacious, it needs to be able to reach the target site, and remain long enough to take effect without being toxic. Therefore it is advantageous to evaluate drug pharmacokinetics study of various drug delivery methods in order to better characterize drug delivery systems and evaluate their efficacy. The broad applicability o f microdialysis sampling to evaluate drug delivery is presented in this dissertation.
There has been rapid growth in the area of pharmacokinetics due to advanced analytical instrumentation. This has allowed for high quality data on blood and plasma pharmacokinetics, however tissue pharmacokinetics data are less precise because o f the lack of reliable techniques to measure tissue drug concentrations. It is especially important to know tissue pharmacokinetics in order to better evaluate drug distribution and delivery to various tissues.
Microdialysis is a powerful analytical technique for the study of in vivo pharmacokinetics and the metabolism of drugs in the extracellular fluid of virtually any tissue, organ or biological fluid. Microdialysis sampling allows for high temporal resolution of drug concentrations in tissues to be made, allowing for drug delivery pharmacokinetics to be obtained from a variety of tissues.
The work presented in this dissertation demonstrates the ability of microdialysis sampling to evaluate the distribution of drugs following two different routes of administration. The transdermal kinetics of a topical application intended for pain relief are evaluated as well as an injectable form of one of the components present in the topical application. Data is obtained on the effectiveness o f each route o f administration in delivering therapeutic levels of drug to the target site.
Ways to prolong the delivery and distribution of a drug for longer pain relief were also investigated. This is done using a delivery microdialysis study that allows for delivery of the analyte of interest while simultaneously monitoring for its distribution in the tissue. More and more research is being done using microdialysis sampling. This has allowed for more pharmaceutical companies to recognize the applicability o f microdialysis sampling and therefore utilize it in their research. The studies in this dissertation demonstrate the ability of microdialysis sampling to provide pharmacokinetics study data that other analytical methods cannot provide.