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Pharmacokinetics of high-dose intravenous melphalan in children and adults with forced diuresis

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  • Original Articles
  • High-dose Melphalan, Pharmacokinetics
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Summary

The pharmacokinetic parameters of the alkylating agent melphalan were determined in 15 children and 11 adults with advanced malignant solid tumors. High IV bolus doses of 140 mg/m2 were given under standard hyperhydration conditions and followed by autologous bone marrow grafting. In all cases the time-concentration curves could be best fitted to a biexponential pattern. A high scattering of drug concentrations was observed in our patients, the disposition half-lives ranging in the whole group from 17.8 to 71.2 min. The areas under the curves also showed a wide variation, ranging from 175 to 682 mg l-1 min-1. In all patients, melphalan levels in plasma were unmeasurable at 8 h or earlier, indicating that bone marrow can be safely reinfused at that time. No difference was apparent between children and adults regarding the drug pharmacokinetics. In each of 11 cerebrospinal fluid samples drawn 45–150 min after melphalan administration, drug levels were unmeasurable.

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References

  1. Alberts DS, Chang SY, Chen HS, Evans TL, Moon TE (1979) Systemic availability of oral melphalan. Cancer Treat Rev 6: 51

    Google Scholar 

  2. Bosanquet AG, Gilby ED (1984) Comparison of the fed and fasting states on the absorption of melphalan in multiple myeloma. Cancer Chemother Pharmacol 12: 183

    Google Scholar 

  3. Brox L, Birkett L (1979) Pharmacology of intravenous melphalan in patients with multiple myeloma. Cancer Treatment Rev 6: 27

    Google Scholar 

  4. Chang SY, Alberts DS, Melnick LR, Walson PD, Salmon SE (1978) High-pressure liquid chromatographic analysis of melphalan in plasma. J Pharm Sci 5: 679

    Google Scholar 

  5. Cornwell GG, Pajak TF, McIntyre OR, Kochwa S, Dosik H (1982) Influence of renal failure on myelosuppressive effects of melphalan: Cancer and leukemia group B experience. Cancer Treatment Rep 66: 475

    Google Scholar 

  6. D'Incalci M, Farina P, Sessa C, Mangioni C, Conter V, Masera G, Rocchetti M, Brambilla Pisoni M, Piazza E, Beer M, Cavalli F (1982) Pharmacokinetics of VP 16 given by different administration methods. Cancer Chemother Pharmacol 7: 141

    Google Scholar 

  7. Gibaldi M, Perrier D (1975) Pharmacokinetics. M Dekker, New York, chap 2

    Google Scholar 

  8. Gomeni R (1984) PHARM, an interactive graphic program for individual and population pharmacokinetic parameters estimation. Comput Biol Med 14: 25

    Google Scholar 

  9. Gouyette A, Hartmann O, Pico JL (1986) Pharmacokinetic of high-dose melphalan in children and adults. Cancer Chemother Pharmacol (in press)

  10. Lott RS, Hayton WL (1978) Estimation of creatinine clearance from serum creatinine concentration. Drug Intell Clin Pharm 12: 140

    Google Scholar 

  11. McElwain TJ, Hedley DW, Burton G, Clink HM, Gordon MY, Jarman M, Juttner CA, Millar JL, Milsted RAV, Prentice G, Smith IE, Spence D, Woods M (1979) Marrow autotransplantation accelerates haematological recovery in patients with malignant melanoma treated with high-dose melphalan. Br J Cancer 40: 72

    Google Scholar 

  12. Pallante SL, Fenselau C, Mennel RG, Brundett RB, Appler M, Rosenshein N, Colvin M (1980). Quantitation by gas chromatography-chemical ionization-mass spectrometry of phenylalanine mustard in plasma of patients. Cancer Res 40: 2268

    Google Scholar 

  13. Taha IAK, Ahmad RA, Gray H, Roberts CI, Rogers HJ (1982) Plasma melphalan and prednisolone concentrations during oral therapy for multiple myeloma. Cancer Chemother Pharmacol 9: 57

    Google Scholar 

  14. Taha IAK, Ahmad RA, Rogers DW, Pritchard J, Rogers HJ (1983) Pharmacokinetics of melphalan in children following high-dose intravenous injection. Cancer Chemother Pharmacol 10: 212

    Google Scholar 

  15. Tattersall MHN, Jarman M, Newlands ES, Holyhead L, Milstead RAV, Weinberg A (1978) Pharmacokinetic of melphalan following oral or intravenous administration in patients with malignant disease. Eur J Cancer 14: 507

    Google Scholar 

  16. Woodhouse KW, Hamilton P, Lennard A, Rawlinsm D (1983) The pharmacokinetic of melphalan in patients with multiple myeloma: an intravenous/oral study using a conventional dose regimen. Eur J Clin Pharmacol 24: 283

    Google Scholar 

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Ardiet, C., Tranchand, B., Biron, P. et al. Pharmacokinetics of high-dose intravenous melphalan in children and adults with forced diuresis. Cancer Chemother. Pharmacol. 16, 300–305 (1986). https://doi.org/10.1007/BF00293997

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  • DOI: https://doi.org/10.1007/BF00293997

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