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.
Urien
S
S
Laboratoire de Pharmacologie, Faculté de Médecine, Créteil, France.
Brée
F
F
Breillout
F
F
Bastian
G
G
Krikorian
A
A
Tillement
J P
JP
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