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Abstract #0938

Determination of Brain Histidine Concentrations and Kinetic Modeling of Human Blood Brain Barrier Transport

Daniel Guo Quae Chong1, Jean-Marc Nuoffer2, Christine Sandra Bolliger1, Peter Vermathen1, Chris Boesch1, Roland Kreis1

1Department of Clinical Research, University Bern, Bern, Switzerland; 2Departement Hmatologie, Onkologie, Infektiologie, Labor-Medizin und Spitalpharmazie (DOLS), Inselspital, Bern, Switzerland

Normal human blood and brain histidine concentrations were measured over a 10 hour period after an oral load. On average, blood histidine concentrations reached a maximum of 3.5 mM while brain histidine peaked at 1.9 mM, 5 hours after blood. Applying the symmetric Michaelis-Menten kinetics resulted in kinetic parameters of maximum transport of 23 nmol/g/min, an apparent Michaelis constant of 2.1 mM and a cerebral metabolization rate of 0.3 nmol/g/min. The complexity of the system investigated and various factors render the data inconclusive upon the appropriate kinetic model and potential subject dependence of the kinetics.