Research Abstracts Online
2008 - March 2009
University of Minnesota Twin Cities
School of Pharmacy
Department of Pharmaceutics
PI: Ronald J. Sawchuk
Analysis of Data From Pharmacokinetic Studies
This researcher is investigating the delivery of antibiotics to the middle ear space for the treatment of infections in an effort to translate this technology for the treatment of otitis media to pediatric patients. The approach utilizes a polymer-based liquid formulation that rapidly forms a gel in contact with the tympanic membrane (TM–ear drum) as the temperature of the formulation increases from ambient to about 28 to 30 degrees Celsius. Antibiotics contained in the formulation may diffuse through the TM and enter the target site, i.e., the middle ear fluid, where concentrations of the antibiotic rise slowly as the gel continues to release the drug, and diffusion of the antibiotic across the middle ear mucosa into blood occurs. Modeling the delivery rate of the antibiotic requires deconvolution of the plasma concentration-time profile using a unit impulse response function. The latter function is obtained by administering a small unit dose of the drug directly in to the middle ear fluid in a separate set of experiments, and characterizing the time course of the antibiotic as it disappears from the target site. Dosage form characteristics and physicochemical properties of the antibiotic molecule determine, in concert, the rate and extent of the entry of the drug into the target site. A knowledge of the susceptibility of the bacteria to the antibiotic, in particular the minimum effective concentration of the antibiotic for the organism in question, will aid in selecting the appropriate delivery rate of the antibiotic and designing the formulation.