Lin, Yvonne SSherry, Tara Catherine2013-07-252015-12-142013-07-252013Sherry_washington_0250O_11562.pdfhttp://hdl.handle.net/1773/23712Thesis (Master's)--University of Washington, 2013The activity of the drug-metabolizing enzyme cytochromes P450 3A (CYP3A) varies up to 20-fold between individuals. The interindividual variability may be due to both genetic variations and factors such as age, diet, concurrent use of multiple medications, disease, pregnancy, and environmental constituents. Phenotyping using endogenous CYP3A biomarkers would allow for direct individual assessments of CYP3A activity. Our goal was to explore the utility of endogenous biomarkers (metabolites of cortisol, cholesterol and vitamin D3) in predicting CYP3A activity as determined by oral midazolam clearance. We found moderate correlations between midazolam oral clearance and plasma 4Beta-hydroxycholesterol/cholesterol, urinary 6Beta-hydroxycortisol/cortisol ratios, and urinary 6Beta-hydroxycortisone/cortisone ratios. We found a poor correlation between midazolam oral clearance and plasma 4Beta,25-dihydroxyvitamin D3/25-hydroxyvitamin D3 ratios. Although these markers were sensitive to CYP3A induction, they were poorly predictive of the fold-change of midazolam oral clearance following rifampin treatment. A better endogenous marker for CYP3A activity is needed.application/pdfen-USCopyright is held by the individual authors.Activity; Biomarkers; CYP3A; EndogenousPharmaceutical sciencespharmaceuticsThesis