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Pharmacokinetics of high-dose cyclophosphamide in patients with metastatic bronchogenic carcinoma

  • Original Articles
  • Pharmacokinetics, High-dose Cyclophosphamide, Bronchogenic Carcinoma
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Summary

Cyclophosphamide (CP) was administered to eight patients with metastatic bronchial carcinoma in escalating doses of 1.5, 2.5, and 3.5 g/m2 at intervals of 3 weeks. The proportion of the administered dose converted into alkylating metabolites was similar for each dose and there was no evidence to suggest that the enzyme system responsible for activating CP was saturated even with the highest dose. Considerable between-patient variation in drug metabolism was observed, but within each patient the fraction metabolised remained constant.

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References

  1. Boughton OD, Brown RD, Bryant R, Burger FJ, Combs CM (1972) Assay of cyclophosphamide. J Pharm Sci 61:97–100

    Google Scholar 

  2. Cohen JL, Jao JY (1970) Enzymatic basis of cyclophosphamide activation by hepatic microsomes of the rat. J Pharmacol Exp Ther 174:206–210

    Google Scholar 

  3. Cohen JL, Jao JY, Jusko WJ (1971) Pharmacokinetics of cyclophosphamide in man. Br J Pharmacol 43:677–680

    Google Scholar 

  4. Connors TA, Cox PJ, Farmer PB (1974) Some studies of the active intermediates formed in the microsomal metabolism of cyclophosphamide and isophosphamide. Biochem Pharmacol 23:115

    Google Scholar 

  5. D'Incalci M, Bolis G, Facchinetti T, Mangioni C, Morasca L, Morazzoni P, Salmona M (1979) Decreased half-life of cyclophosphamide in patients under continual treatment. Eur J Cancer 15:7–10

    Google Scholar 

  6. Field RB, Gang M, Kline I, Venditti JM, Waravdekar VS (1972) The effect of phenobarbital or 2-diethylaminoethyl 2,2 diphenylvalerate on the activation of cyclophosphamide in vivo. J Pharm Exp Ther 180:475–483

    Google Scholar 

  7. Foley GE, Friedman OM, Dralet BP (1961) Studies on the mechanisms of action of Cytoxan: evidence of activation in vivo and in vitro. Cancer Res 21:57–63

    Google Scholar 

  8. Grochow LB, Colvin M (1979) Clinical pharmacokinetics of cyclophosphamide. Clin Pharmacol 4:380–394

    Google Scholar 

  9. Hansen HH, Rørth M (1981) In: Pinedo HM (ed) Cancer chemotherapy 1981. Excerpta Medica, Amsterdam Oxford, pp 279–296

    Google Scholar 

  10. Hepper GW, Vessell ES, Lipton A, Harvey HA, Williamson GR, Schenker S (1980) Disposition of aminopyrine, anti-pyrine, diazepam and indocyanine green in patients with liver disease or on anti-convulsant therapy. J Lab Clin Med 90:440–556

    Google Scholar 

  11. Hill DL, Laster WRJ, Struck RF (1972) Enzymatic metabolism of cyclophosphamide and nicotine and production of toxic cyclophosphamide metabolite. Cancer Res 32:658–665

    Google Scholar 

  12. Jardine I, Fenselau C, Appler MN, Kan RB, Brundrett RB, Calvin M (1978) Quantitation by gas chromatography-chemical ionization mass spectrometry of cyclophosphamide, phosphoramide mustard, and nornitrogen mustard in the plasma and urine of patients receiving cyclophosphamide therapy. Cancer Res 38:408–415

    Google Scholar 

  13. Marinello AJ, Gurtoo HL, Struck RF, Paul P (1978) Denaturation of cytochrome P 450 by cyclophosphamide metabolites. Biochem Biophys Res Commun 83:1347–1353

    Google Scholar 

  14. Milstead RA, Jarman M (1982) Metabolism of high doses of cyclophosphamide. Cancer Chemother Pharmacol 8:311–313

    Google Scholar 

  15. Mouridsen HT, Faber O, Skovsted L (1974) The biotransformation of cyclophosphamide in man: analysis of the variation in normal subjects. Acta Pharmacol Toxicol 35:98–106

    Google Scholar 

  16. Mouridsen HT, Faber O, Skovsted L (1976) The metabolism of cyclophosphamide: dose dependency and the effect of long-term treatment with cyclophosphamide. Cancer 37:665–670

    Google Scholar 

  17. Pantarotto C, Bossi A, Belvedere G, Martini A, Donelli MG, Frigerio A (1974) Quantitative GLC determination of cyclophosphamide and isophosphamide in biological specimens. J Pharm Sci 63:1554–1558

    Google Scholar 

  18. Sladek NE (1971) Metabolism of cyclophosphamide by rat hepatic microsomes. Cancer Res 31:901–908

    Google Scholar 

  19. Williams RL, Benet LZ (1980) Drug pharmacokinetics in cardiac and hepatic disease. Annu Rev Pharmacol Toxicol 20:389–413

    Google Scholar 

  20. Williams RL, Mamleok RD (1980) Hepatic disease and drug pharmacokinetics. Clin Pharmacokin 5:528–547

    Google Scholar 

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Wilkinson, P.M., O'Neill, P.A., Thatcher, N. et al. Pharmacokinetics of high-dose cyclophosphamide in patients with metastatic bronchogenic carcinoma. Cancer Chemother. Pharmacol. 11, 196–199 (1983). https://doi.org/10.1007/BF00254204

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  • DOI: https://doi.org/10.1007/BF00254204

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