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Clinical Chemistry 35: 56-63, 1989;
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Clinical Chemistry, Vol 35, 56-63, Copyright © 1989 by American Association for Clinical Chemistry

Distribution of cyclosporin A metabolites among plasma and cells in whole blood: effect of temperature, hematocrit, and metabolite concentration

GL Lensmeyer, DA Wiebe and IH Carlson
Clinical Laboratories, University of Wisconsin Hospital, Madison 53792.

Drug-free whole-blood samples supplemented with the cyclosporines and samples from 10 transplant patients receiving cyclosporin A (CsA) were equilibrated at 4, 22, and 37 degrees C for 2.5 h; the plasma and cells were separated; and the fractions were assayed by high-performance liquid chromatography (HPLC). Partitioning of CsA and metabolites among plasma and cells was diverse and not always predictable for patients' samples. Overall, although widely variable, greater than 50% of the total concentration of metabolites M1, M8, M9, M10, M16, M17, U1, U8, and U9 in whole blood was associated with the cells, whereas greater than 50% of M13, M18, M21, M25, M26, M203-218, U2, U3, U4, U5, U6, and U7 was associated with plasma. A decrease in hematocrit from 47.8% to 24%, an increase of the sample's temperature (from 4 to 37 degrees C), or an increase in analyte concentration (usually greater than 500 micrograms/L for selected metabolites) increased the relative portion associated with plasma in a nonlinear fashion. Parent CsA was most influenced by these changes; its relative concentrations in plasma varied from 18% to 50%. These data support the preferential use of whole blood for therapeutic monitoring of "cyclosporines." Through additional studies, we suggest possible mechanisms affecting the distribution phenomenon and ascribe chemical structure-distribution relationships.


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