Summary
High-dose cyclophosphamide is used immediately after total body irradiation (TBI) in conditioning for bone marrow transplantation (BMT). Possible interactions of the two treatment modalities were sought by measuring the blood pharmacokinetics of CP and 4-hydroxy-cyclophosphamide (4-HOCP) in patients undergoing BMT.
There was a non-significant trend to a shorter half-life of CP compared to reported values. Exposure to 4-HOCP, the major metabolite of CP, did not appear to be altered by prior TBI of the patient.
Similar content being viewed by others
References
Wagner T, Heydrich D, Jork T, Voelcker G, Hohorst HJ (1981) Comparative Study on human pharmacokinetics of activated ifosfamide and cyclophosphamide by a modified fluorometric test. J Cancer Res Clin Oncol 100: 95–104
Buice RG, Veit BC, McAlpin SE, Gurley BJ, Sidhu P (1984) Effects of total body irradiation followed by bone marrow transplantation on the disposition kinetics of mitomycin-C in the rat. Res Commun Chem Pathol Pharmacol 44: 401–410
Yukawa O, Nakazawa T (1973) Sites of X-irradiation induced damage in the microsomal drug metabolizing enzyme system of rat liver during development. Radiat Res 56: 140–149
Knott JCA, Wills ED (1974) The role of testosterone in the regulation of oxidative drug metabolism in normal and irradiated animals. Biochem Pharmacol 23: 793–800
Kergonou JF, Braquet M, Rocquet G (1980) Influence of whole-body gamma irradiation upon rat liver mitochondrial fractions. Radiat Res 88: 377–384
Yukawa O, Nakazawa T (1980) Radiation-induced lipid peroxidation and membrane-bound enzymes in liver microsomes. Int J Radiat Biol 37: 621–631
Yukawa O, Nagatsuka S, Nakazawa T (1983) Reconstitution studies on the involvement of radiation-induced lipid peroxidation in damage to membrane enzymes. Int J Radiat Biol 43: 391–398
Bernard P, Neveux Y, Rocquet G, Drouet J (1980) Studies of microsomal glucose-6-phosphatase on liver of irradiated rats. Enzyme 25: 250–257
Bitny-Szlachto S, Szyszko A (1979) Effects of whole body X-ray irradiation on induction by phenobarbital of rat liver glucose-6-phosphate dehydrogenase and glutathione reductase. Acta Pol Pharm 36: 117–122
Wills ED, Wilkinson AE (1970) Effects of irradiation on sub-cellular components II. Hydroxilation in the microsomal fraction. Int J Radiat Biol 17: 229–236
DuBois KP (1967) Inhibition by radiation of the development of drug detoxification enzymes. Radiat Res 30: 342–350
Nair V (1967) Modification of pharmacological activity following x-irradiation. Radiat Res 30: 359–373
Bodo K, Benkö G (1986) Untersuchungen der Monoaminooxydase-Aktivität des Gehirns und der Leber von 60Co-gammabestrahlten Mäusen bei Verwendung einer Strahlenschutzverbindung. Radiobiol Radiother 27: 457–461
Nesterova TA, Smirnova TN, Tutochkina LT (1983) Hydroxilating activity of rat liver microsomes upon formation of proteins of acute phase during acute radiation sickness. Radiobiologiia 23: 672–675
Hagenbeek A, Martens AC (1987) Conditioning regimens prior to bone marrow transplantation in acute myelocytic leucemia. Bone Marrow Transpl 2 [Suppl]. 37–38 (abstract)
Hagenbeek A, Martens AC (1983) Efficacy of high-dose cyclophosphamide in combination with total-body irradiation in the treatment of acute myelocytic leukemia: studies in a relevant rat model. Cancer Res 43: 408–412
Gale R, Champlin R (1986) Bone marrow transplantation in acute leukemia. Clin Haematol 15: 851–872
Schuler U, Ehninger G, Wagner R (1987) Repeated high-dose cyclophosphamide administration in bone marrow transplantation: exposure to activated metabolites. Cancer Chemother Pharmacol 20: 248–252
Alarcon RA (1968) Fluorometric determination of acrolein and related compounds with m-aminophenol. Anal Chem 40: 1704–1708
Heinzel G (1982) Salient points of various programs. TOPFIT, in Bozler G, Rossum JM: (eds): Pharmacokinetics during drug development: data analysis and evaluation techniques. Fischer, Stuttgart, p 207–211
Bagley CM, Bostick FW, DeVita VT (1973) Clinical pharmacology of cyclophosphamide. Cancer Res 33: 226–233
Sladeck NE, Priest J, Doeden D, Mirocha CJ, Pathre S, Krivit W (1980) Plasma half-life and urinary excretion of cyclophosphamide in chidren. Cancer Treat Rep 64: 1061–1066
Graham MI, Shaw IC, Souhami RL, Sidau B, Harper PG, Mclean AEM (1983) Decreased plasma half-life of cyclophosphamide during repeated high-dose administration. Cancer Chemother Pharmacol 10: 192–193
Lind MJ, Margison JM, Cerny T, Thatcher N, Wilkinson PM (1989) Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma. Cancer Res 49: 753–757
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schuler, U., Waidelich, P., Kolb, H. et al. Pharmacokinetics and metabolism of cyclophosphamide administered after total body irradiation of bone marrow transplant recipients. Eur J Clin Pharmacol 40, 521–523 (1991). https://doi.org/10.1007/BF00315233
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00315233