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Clinical Chemistry 39: 213-217, 1993;
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Clinical Chemistry, Vol 39, 213-217, Copyright © 1993 by American Association for Clinical Chemistry

Distribution of cyclosporin G (NVa2 cyclosporin) in blood and plasma

RW Yatscoff, N Honcharik, M Lukowski, J Thliveris, P Chackowsky and C Faraci
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.

We report here on the distribution of cyclosporin G (CsG), an analog of cyclosporin A, in whole blood. CsG has a temperature-dependent distribution between erythrocytes (RBCs) and plasma. After 30 min at 37 degrees C, the plasma/whole blood and plasma/RBC ratios were relatively constant (0.7-0.8) up to CsG at 1000 micrograms/L. At 5000 micrograms/L, this ratio increased to 1.0-1.1 for plasma/whole blood and 1.7 for plasma/RBC. The primary CsG metabolites GM1 and GM9 were sequestered within RBCs to a greater extent than was the parent drug. In whole blood, approximately 2% of CsG was bound to granulocytes, 6% to lymphocytes, and 50-55% to RBC, and 35-40% was found in the plasma fraction. The free fraction of the drug as determined by ultracentrifugation was 5-6% and 13-17% of total drug at 37 and 4 degrees C, respectively. In plasma the drug was primarily associated with high-density lipoprotein (50-60%) and to a lesser degree with low- density (20-30%) and very-low-density (10%) lipoproteins.


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P. H. Hinderling
Red Blood Cells: A Neglected Compartment in Pharmacokinetics and Pharmacodynamics
Pharmacol. Rev., September 1, 1997; 49(3): 279 - 295.
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