Summary
Busulfan kinetics were studied in the rat plasma and brain after an I.P. dose of14C-busulfan or busulfan (15 mg/kg). The distribution of busulfan to the brain was rapid and the ratio brain / plasma concentration was 0.74 during the time-course of busulfan.
The elimination half-lives in plasma and brain were 3h for intact busulfan and 8h for the14C-radioactivity. The radioactivity remaining in plasma and brain after 24h was mostly busulfan metabolites e.g. sulfolane, 3-hydroxysulfolane and tetrahydrothiophene-1-oxide as identified by gas chromatography-mass spectrometry. The protein binding to rat plasma was low (9.2 +- 4.4%).
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Santos G.W., Tutschka P.J., Brookmeyer R., Saral R., Beschomer W.E., Bias W.B., et al. (1983): Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide. N. Engl. J. Med., 309, 1347–1353.
Tutschka P.J., Copelan E.A., Klein J.P. (1987): Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood, 70, 1382–1388.
Parkman R., Rappeport J.M., Hellman S., Lipton J., Smith B., Geha R., Nathan D.G. (1984): Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogeneic bone marrow transplantation. Blood, 64, 852–857.
Stephani U., Rating D., Korinthenberg R., Siemes H., Riehm H., Hanefeld F. (1983): Radiation-related disturbance of blood/brain barrier during therapy of acute lymphoblastic leukemia. Lancet, II, 1036–1037.
Deeg H.J., Sullivan K.M., Buckner C.D., Starb R., Appelbaum F.R., Clift R.A., Doney K., Sanders J.E., Witherspoon R.P., Thomas E.D. (1986): Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation. Bone Marrow Transplant., 1, 151–157.
Hobbs J.R., Hugh-Jones K., Shaw P.J., Downie C.J.C., Williamson S. (1986): Engraftment rates related to busulphan and cyclophosphamide dosage for displacement bone marrow transplants in fifty children. Bone Marrow Transplant., 1, 201–208.
Peng C-T. (1957): Distribution and metabolic fate of S35-labeledmyleran (busulfan) in normal and tumor-bearing rats. J. Pharmacol., 120, 229–238.
Trams E.G., Nadkami M.V., deQuattro V., Maengwyn-Davies G.D., Smith P.K. (1959): Dimethanesulphonoxybutane (myleran) preliminary studies on distribution arid metabolic fate in the rat. Biochem. Pharmacol., 2, 7–16.
Hassan M., Ehrsson H. (1986): Degradation of busulfan in aqueous solution. J. Pharm. Biomed. Anal., 4, 95–101.
Hassan M., Ehrsson H. (1987): Urinary metabolites of busulfanin the rat. Drug Metab. Dispos., 15, 399–402.
Hassan M., Ehrsson H. (1983): Gas chromatographic detennination of busulfan in plasma with electron-capture detection. J. Chromatogr., 277, 374–380.
Ehrnebo M., Agurell S., Boreus L.O., Gordon E., Lonroth U. (1974): Pentazocine binding to blood cells and plasma proteins. Clin. Pharmacol. Ther., 16, 424–429.
Gjedde A. (1986): The selective barrier between blood and brain. Trends Biochem. Sci., 11, 525–527.
Hansh C., Björkroth J.P., Leo A. (1987): Hydrophobicity and central nervous system agents: On the principle of minimal hydrophobicity in drug design. J. Pharm. Sci., 76, 663–687.
Ehrsson H., Lönroth U. (1982): Degradation of melphalan in aqueous solution-influence of human albumin binding. J. Pharm. Sci., 71, 826–827.
Ehrsson B., Lönroth U., Wallin I., Ehmebo M., Nilsson S.O. (1981): Degradation of chlorambucil in aqueous solution — influence of human albumin binding. J. Pharm. Pharmaeol., 33, 313–315.
Greig N.H., Sweeney D.J., Rapoport S.I. (1988): Comparative brain and plasma pharmacokinetics and anticancer activities of chlorambucil and melphalan in the rat. Cancer Chemother. Pharmacol., 21, 1–8.
Shapiro W.R., Young D.F., Mehta B.M. (1975): Methotrexate: Distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N. Engl. J. Med., 293, 161–166.
Oldendorf W.H. (1983): Aspects of blood-brain barrier in clinical brain imaging. Acta Neuropathol. (Berl.) Suppl., VIII, 111–117.
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Hassan, M., Ehrsson, H., Wallin, I. et al. Pharmacokinetic and metabolic studies of busulfan in rat plasma and brain. Eur. J. Drug Metab. Pharmacokinet. 13, 301–305 (1988). https://doi.org/10.1007/BF03190094
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DOI: https://doi.org/10.1007/BF03190094