Vinorelbine high-affinity binding to human platelets and lymphocytes: distribution in human blood.
Using [3H]-vinorelbine, we demonstrated the presence of saturable and time-dependent high-affinity binding sites on human platelets and lymphocytes. The dissociation constant and binding-site values observed were 200 +/- 38 nM, 20.0 +/- 2.2 amol/platelet, and 155 +/- 20 amol/lymphocyte, respectively. Among other blood components, saturable low-affinity binding of vinorelbine to alpha 1-acid glycoprotein, serum albumin, and lipoproteins was observed. The binding to erythocytes was nonsaturable. Given the relative concentrations of these carriers, vinorelbine mainly distributes in the platelet compartment in blood (> 70%), and the amount of free vinorelbine in plasma relative to the total amount in blood is < 2%. It is suggested that because of the preferential retention of vinorelbine by platelets, variations in the platelet count are very likely to produce changes in the free blood fraction of vinorelbine.
Laboratoire de Pharmacologie, Faculté de Médecine, Créteil, France.
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Urien
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Brée
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Breillout
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Bastian
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Krikorian
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Tillement
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood*; D011485:Protein Binding; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000097:blood; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D001798:Blood Proteins; D014747:Vinblastine; D000077235:Vinorelbine