Pharmaceutisch Weekblad

, Volume 11, Issue 6, pp 218–223 | Cite as

The bioavailability of three altretamine formulations

  • E. A. Runhaar
  • J. P. Neijt
  • J. J. M. Holthuis
  • D. de Vos
Original Articles


The bioavailability of two altretamine preparations was studied in a randomized cross-over design. The two preparations were compared with a third in a parallel design. Dissolution differences between the preparations were observed, which could give rise to differences in bioavailability caused by the extensive first-pass effect of altretamine. Thein vivo data showed a trend to differences in bioavailability.


Altretamine Biological availability Metabolism Pharmacokinetics 


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  1. 1.
    Weiss RB. The role of hexamethylmelamine in advanced ovarian carcinoma treatment. Gynecol Oncol 1981;12:141–9.PubMedGoogle Scholar
  2. 2.
    Goldsweig HG, Edgerton F, Smith Redden C, Takita H, DeLaGarza JG, Bisel HF. Hexamethylmelamine as a single agent in the treatment of small-cell carcinoma of the lung. Am J Clin Oncol 1982;5:267–72.PubMedGoogle Scholar
  3. 3.
    Ross D, Langdon SP, Gescher A, Stevens MFG. Studies of the mode of action of antitumour triazenes. V. The correlation of thein vitro cytotoxicity andin vivo antitumour activity of hexamethylmelamine analogues with their metabolism. Biochem Pharmacol 1984;33:1131–6.PubMedGoogle Scholar
  4. 4.
    D'Incalci M, Beggiolin G, Sessa C, Mangioni C. Influence of ascites on the pharmacokinetics of hexamethylmelamine andN-demethylated metabolites in ovarian cancer patients. Eur J Cancer Clin Oncol 1981;12:1331–5.Google Scholar
  5. 5.
    D'Incalci M, Farina P, Sessa C, Mangioni C, Garattini S. Hexamethylmelamine distribution in patients with ovarian and other pelvic cancers. Cancer Treat Rep 1982;66:231–5.PubMedGoogle Scholar
  6. 6.
    D'Incalci M, Bolis G, Mangioni C, Morasca L, Garattini S. Variable oral absorption of hexamethylmelamine in man. Cancer Treat Rep 1978;62:2117–9.PubMedGoogle Scholar
  7. 7.
    Worzalla JF, Kaiman BD, Johnson BM, Ramirez G, Bryan GT. Metabolism of hexamethylmelamine-ring-14C in rats and man. Cancer Res 1974;34:2669–74.PubMedGoogle Scholar
  8. 8.
    Worzalla JF, Johnson BM, Ramirez G, Bryan GT.N-Demethylation of the antineoplastic agent hexamethylmelamine by rats and man. Cancer Res 1973;33:2810–5.Google Scholar
  9. 9.
    Klippert PJM, Hulshoff A, Mingels M-JJ, Hofman G, Noordhoek J. Low oral bioavailability of hexamethylmelamine in the rat due to simultaneous hepatic and intestinal metabolism. Cancer Res 1983;43:3160–4.PubMedGoogle Scholar
  10. 10.
    Hulshoff A, Neijt JP, Smulders CFA, Van Loenen AC, Pinedo HM. Determination of hexamethylmelamine and metabolites in plasma or serum by gas-liquid chromatography with a nitrogen-sensitive detector. J Chromatogr 1980;181:363–71.PubMedGoogle Scholar
  11. 11.
    McVie JG, Simonetti GPC, Stevenson D, et al. The bioavailability of Tamoplex® (tamoxifen). Part 1. A pilot study. Methods Find Exp Clin Pharmacol 1986;8:505–12.PubMedGoogle Scholar
  12. 12.
    Guelen PJM, Stevenson D, Briggs RJ, De Vos D. The bioavailability of Tamoplex® (tamoxifen). Part 2. A single dose cross-over study in healthy male volunteers. Methods Find Exp Clin Pharmacol 1987;9:685–90.PubMedGoogle Scholar
  13. 13.
    Van de Vaart-van Zutphen HPC, Smulders CFA, Renema J, Hulshoff A. Hexamethylmelamine and hexamethylmelamine hydrochloride. Pharm Weekbl [Sci] 1982;4:25–31.Google Scholar
  14. 14.
    Barnes TC, Frances S. Toxicity of hexamethylmelamine (NSC-13875) in rats. Arch Int Pharmacodyn 1966;160:8–95.Google Scholar
  15. 15.
    Rodda BE, Davis DL. Determining the probability of an important difference in bioavailability. Clin Pharmacol Ther 1980;28:247–52.PubMedGoogle Scholar
  16. 16.
    Fluehler H, Hirtz J, Moser HA. An aid to decision making in bioequivalence assessment. J Pharmacokinet Biopharm 1981;9:235–43.PubMedGoogle Scholar
  17. 17.
    Fluehler H, Grieve AP, Mandallaz D, Mau J, Moser HA. Bayesian approach to bioequivalence assessment: an example. J Pharm Sci 1983;72:1178–81.PubMedGoogle Scholar
  18. 18.
    Hauck WW, Anderson S. A new statistical procedure for testing equivalence in two group comparative bioavailability trials. J Pharmacokinet Biopharm 1984;12:83–91.PubMedGoogle Scholar
  19. 19.
    Steinijans VW, Diletti E. Statistical analysis of bioavailability studies: parametric and nonparametric confidence intervals. Eur J Clin Pharmacol 1983;24:127–36.PubMedGoogle Scholar
  20. 20.
    Steinijans VW, Diletti E. Generalization of distribution free confidence intervals for bioavailability ratios. Eur J Clin Pharmacol 1985;28:85–8.Google Scholar
  21. 21.
    Grizzle JE. The two-period change-over design and its use in clinical trials. Biometrics 1965;21:467–80.PubMedGoogle Scholar
  22. 22.
    Grizzle JE. The two-period change-over design and its use in clinical trials. Correction. Biometrics 1974;30:727.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1989

Authors and Affiliations

  • E. A. Runhaar
    • 1
  • J. P. Neijt
    • 2
  • J. J. M. Holthuis
    • 3
  • D. de Vos
    • 4
  1. 1.Röpcke-Zweers HospitalAA Hardenbergthe Netherlands
  2. 2.Department of Internal Medicine, Division of OncologyUniversity Hospital UtrechtGA Utrechtthe Netherlands
  3. 3.Department of PharmacyUniversity of Utrechtthe Netherlands
  4. 4.Medical DepartmentPharmachemie BVRN Haarlemthe Netherlands

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