Abstract
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 alpha1-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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Böyum A (1968) Isolation of leucocytes from human blood. Scand J Clin Lab Invest 21:9–50
Donigan DW, Owellen RJ (1973) Interaction of vinblastine, vincristine and colchicine with serum proteins. Biochem Pharmacol 22: 2113–2119
Gout PW, Wijcik LL, Beers CT (1978) Differences between vinblastine and vincristine in distribution in the blood of rats and binding by platelets and malignant cells. Eur J Cancer 14:1167–1178
Fitos I, Visy J, Simonyi M (1991) Binding of vinca alkaloid analogues to human serum albumin and to alpha1-acid glycoprotein. Biochem Pharmacol 41:377–383
Krikorian A, Rahmani R, Bromet M, Bore P, Cano JP (1989) Pharmacokinetics and metabolism of Navelbine. Semin Oncol 16:21–25
Masquelier M, Vitols S, Peterson S (1986) Low-density lipoprotein as a carrier of antitumoral drugs: in vivo fate of drug-human lowdensity lipoprotein complexes in mice. Cancer Res 46:3842–3847
Steele WH, King DJ, Barber HE, Hawksworth GM, Dawson AA, Petrie JC (1983) The protein binding of vinblastine in the serum of normal subjects and patients with Hodgkin's disease. Eur J Clin Pharmacol 24:683–687
Tillement JP, Houin G, Zini R, Urien S, Albengres E, Barré J, Lecomte M, D'Athis P, Sébille B (1984) The binding of drugs to biological macromolecules in plasma. Recent advances and therapeutic significance. Adv Drug Res 13:59–94
Urien S, Riant P, Renouard A, Coulomb A, Rocher I, Tillement JP (1988) Binding of indapamide to serum proteins and erythrocytes. Biochem Pharmacol 37:2963–2966
Urien S, Morin D, Renouard A, Rocher I, Tillement JP (1988) Variation in serum binding of tertatolol mediated by disease-induced modification of alpha1-acid glycoprotein concentration. Eur J Clin Pharmacol 34:381–385
Vitols SG, Masquelier M, Peterson CO (1985) Selective uptake of a toxic lipophilic anthracycline derivative by the low-density lipoprotein receptor pathway in cultured fibroblasts. J Med Chem 28: 451–454
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Urien, S., Brée, F., Breillout, F. et al. Vinorelbine high-affinity binding to human platelets and lymphocytes: distribution in human blood. Cancer Chemother. Pharmacol. 32, 231–234 (1993). https://doi.org/10.1007/BF00685841
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00685841