Summary
The interactions of S12363 with human plasma proteins have been investigatedin vitro by an erythrocyte partitioning technique that allows a quantitative estimation of the plasma and erythrocytes binding. S12363 was 85–95% plasma-bound and 97–98% blood-bound. The main binding protein in plasma was alpha-acid glycoprotein, with a binding constant of 0.6·106 M−1, accounting for 70% of total S12363 in plasma. Owing to extensive binding to platelets (40–50% of total blood amount), S12363 was mainly distributed in the non plasma blood compartment, with blood-to-plasma concentrations ratio of 1.2–1.4. These results indicate that,in vivo, the fraction of blood S12363 available for tissue diffusion, i.e., the free drug fraction in blood, should depend on both alpha1-acid glycoprotein concentration in plasma and blood platelet count.
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Pierré A, Kraus-Berthier L, Atassi G, Cros S, Poupon MF, Lavielle G, Berlion M, Bizzari JP: Preclinical antitumor activity of a new Vinca alkaloid derivative, S12363. Cancer Res 51:2312–2318, 1991
Donigan DW, Owellen RJ: Interaction of vinblastine, vincristine and colchicine with serum proteins. Biochem Pharmacol 22:2113–2119, 1973
Steele WH, King DJ, Barber HE, Hawksworth GM, Dawson AA, Petrie JC: The protein binding of vinblastine in the serum of normal subjects and patients with Hodgkin's disease. Eur J Clin Pharmacol 24:683–687, 1983
Gout PW, Wijcik LL, Beers CT: 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, 1978
Tillement JP, Houin G, Zini R, Urien S, Albengres E, Barré J, Lecomte M, D'Athis P, Sébille B: The binding of drugs to biological macromolecules in plasma. Recent advances and therapeutic significance. Adv Drug Res 13:59–94, 1984
Urien S, Zini R, Lemaire M, Tillement JP: Assessment of cyclosporine A interactions with human plasma lipoproteinsin vitro andin vivo in the rat. J Pharmacol Exp Ther 253:305–309, 1990
Maulard C, Urien S, Bastian G, Tillement JP: Binding of retelliptine, a new antitumoral agent, to serum proteins and erythrocytes. Biochem Pharmacol 40:895–898, 1990
Urien S, Riant P, Renouard A, Coulomb A, Rocher I, Tillement JP: Binding of indapamide to serum proteins and erythrocytes. Biochem Pharmacol 37:2963–2966, 1988
Böyum A: Isolation of leucocytes from human blood. Scand J Clin Lab Invest 21:9–50, 1968
Fitos I, Visy J, Simonyi M: Binding of vinca alkaloids analogues to human serum albumin and to alphal-acid glycoprotein. Biochem Pharmacol 41:377–383, 1991
Ings RMJ, Lelièvre E, Ardiet C, Clavel M, Leyvraz S, Minaidis D, Lokiec F, Turpin F, Solere P, Lucas C: The pharmacokinetics and pharmacodynamics of a new vinca alkaloid, S12363, using data from a phase 1 tolerance study in man. Xenobiotica (in press) 1992
Wathne KO, Carlander B, Norum KR, Blomhoff R: Uptake of retinyl ester in HL-60 cells via the low density lipoprotein receptor pathway. Biochem J 257:239–244, 1989
Masquelier M, Vitols S, Peterson S: Low-density lipoprotein as a carrier of antitumoral drugs:in vivo fate of drug-human low-density lipoprotein complexes in mice. Cancer Res 46:3842–3847, 1986
Vitols S, Angelin B, Ericsson S, Gahrton G, Juliusson G, Masquelier M, Paul C, Peterson C, Rudling M, Soderberg-Reid K, Tidefelt U: Uptake of low density lipoproteins by human leukemic cellsin vivo: relation to plasma lipoprotein levels and possible relevance for selective chemotherapy. Proc natl Acad Sci USA 87:2598–2602, 1990
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Urien, S., Bastian, G., Lucas, C. et al. Binding of a new vinca alkaloid derivative, S12363, to human plasma proteins and platelets. Usefulness of an erythrocyte partitioning technique. Invest New Drugs 10, 263–268 (1992). https://doi.org/10.1007/BF00944179
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DOI: https://doi.org/10.1007/BF00944179