BENZPHETAMINE METABOLISM AS A PROBE OF DRUG METABOLISM BY TISSUE BIOPSISE FROM TRANSPLANT PATIENTS. Kimberlie A. Richardson; and mentor, Dr. Marguerite Coomes, Department of Biochemistry, Howard University Washington, DC. When a pharmaceutical agent is administered to transplant patients, it is important to be aware of the drug's effective range in order to ensure optimum therapeutic results. Recently, two immunosuppressants, cyclosporine A and FK506, have been used to reduce chronic rejection of transplanted organs. But FK506 is gaining increased popularity because of its ability to reverse ongoing rejection in animal models, inhibit cell-mediated and humoral response, and cause fewer actue rejections. High concentrations of FK506 in the blood plasma yields toxic effects, including renal failure and stroke. Levels of the drug below the effective range in the plasma cause rejection rates to increase. Cytochrome P450 (P450) is a family of heme proteins in most cells, It activates/inactivates therapeutic agents. The high levels of P450 metabolize drugs at an increased rate and reduce therapeutic plasma levels. When P450 is low, the methabolism of drugs is slower, causing clinical side-effects due primarily to toxic high concentrations of the parent drug. Drug induction of P450 stimulates metabolism of other drugs. A recent study suggest that FK506 reduces the amount of P450 in rats (S. Vincent, Bio-chemical Pharmacology, 41:1325-1330, 1991). This could lead to reduce metrabolism of FK506 and other drugs. Due to the difficulty of using FK506 as a sustrate, benzphetamine is used as a model compound. This investigation was designed to determine whether benzphentamine metabolism in very small amounts of human tissue from liver biopsies could be measured.			The overal reaction to convert benzphetamine to formaldehyde and another product requires a catalyst (P450). It was determined that formaldehyde formation, indicating the amount of P450 in the tissue specimen, could be measured in human liver biopsies. The amount of protien in each biopsy (mg of protein) was also determined. Results from further studies will show whether human liver is affected by FK506 in the same way as the rat liver. Kimderlie Andreas Richardson, a May 1996 graduate who was a chemistry major and mathematics minor, is originally from Atlanta. Richardson will attend Howard's Graduate School od Arts and Sciences, Department of Pharmacology. During her undergraduate studies at Howard University, Richardson took courses to fulfill the requirments for American Chemical Society certification as a chemistry major. Richardson plans to pursue an M.D./Ph.D. degree in graduate school. Before enrolling in Howard in 1992, Richardson researched the molecular and structural effects of an antibiotic on tissue regeneration at Morehouse and Morris Brown College for four years. Her research goals include applying the basic knowledge of chemistry and biology to life systems. McNair Alumni