Semester

Spring

Date of Graduation

2003

Document Type

Thesis

Degree Type

MS

College

School of Pharmacy

Department

Pharmaceutical Sciences

Committee Chair

Patrick S. Callery.

Abstract

One of the difficulties in drug delivery is transporting the compound of interest to the target organ while minimizing exposure to the rest of the body. Intravenous administration is effective in the delivery of drugs and results in high bioavailability leading to very rapid systemic distribution. Oral dosing of drugs is the most popular route because of its ease of administration, but it is subject to first pass metabolism by the liver which can greatly reduce the bioavailability of the parent compound. Patients undergoing hysterectomy were recruited for a study in which they were anesthetized and 5 mg of diazepam in gel was applied directly to the cervix by a patented drug delivery device (CerviPrep(TM)) consisting of a modified plastic syringe with a rounded cup on the end. The operation was then begun and blood samples were taken from a peripheral vein at 0, 5, 10, 15, and 30 minutes during drug administration. Samples were also taken from the uterine vein and uterine capillary bed at 30--45 minutes during drug administration had begun. Red blood cells were separated from plasma and the plasma was analyzed for the presence of diazepam using an assay based on gas chromatography/mass spectrometry using stable isotopically labeled internal standards. In some of the patients, there was a measurable concentration of diazepam in uterine capillary blood following cervical administration, and some patients had greater than a ten-fold higher concentration in uterine blood than peripheral blood. The studies serve as a starting point for the development of delivery systems for other drugs, especially toxic anti-cancer drugs, delivered directly through the cervix and to the uterus. The results indicate that it is possible to deliver a drug locally to the cervix through a transdermal process and observe blood concentrations that are higher than those from peripheral blood.

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