Distribution of cyclosporin G (NVa2 cyclosporin) in blood and plasma.
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.
Yatscoff
R W
RW
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
Honcharik
N
N
Lukowski
M
M
Thliveris
J
J
Chackowsky
P
P
Faraci
C
C
D016572:Cyclosporine; D003524:Cyclosporins / Q000097:blood* / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D013696:Temperature; D014461:Ultracentrifugation
D003524:Cyclosporins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C045571:cyclosporin G; D016572:Cyclosporine