Skip to main content
SpringerLink
Log in

Pharmacokinetic study of indicine N-oxide in pediatric cancer patients

  • Original Articles
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Pharmacokinetics of the experimental antitumor agent indicine N-oxide were investigated in a group of 23 pediatric cancer patients. Plasma elimination of indicine N-oxide was best described by a two-compartment open model. The mean plasma distribution phase half-life, plasma elimination phase half-life, and plasma clearance were 8 min, 84 min, and 62 ml/min/m2 (2.1 ml/min/kg), respectively. One patient with renal impairment had an abnormally long plasma elimination phase half-life (275 min) and reduced plasma clearance (17 ml/min/m2). Plasma elimination phase half-life values increased and plasma clearance values decreased with increasing age of the pediatric patients. Plasma elimination of indicine N-oxide was more rapid in this group of children than in adults who had previously received the drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ames MM, Powis G (1978) Determination of indicine N-oxide and indicine in plasma and urine by electron-capture gas-liquid chromatography. J Chromatogr 166:519

    Google Scholar 

  2. Bull LB, Culvenor CCJ, Dick AT (1968) The pyrrolizidine alkaloids; their chemistry, pathogenicity and other biological properties. In: Neuberger A, Tatum EL (eds) Frontiers of Biology, vol 9. Wiley, New York, p 1

    Google Scholar 

  3. Castles TR, Snyder JL, Lee C, Folk RM, Cooney DA (1976) Toxicity of indicine N-oxide (NSC 132319) in mice, dogs and monkeys. Chem Abs 84:54233

    Google Scholar 

  4. Culvenor CCJ (1968) Tumor inhibitory activity of pyrrolizidine alkaloids. J Pharm Sci 57:1112

    Google Scholar 

  5. D'Incalci M, Farina P, Sessa C, Mangioni C, Conter V, Masera G, Rocchetti M, Pisoni MB, Piazza E, Beer M, Cavalli F (1982) Pharmacokinetics of VP16-213 given by different administration methods. Cancer Chemother Pharmacol 7:141

    Google Scholar 

  6. Kovach JS, Ames MM, Powis G, Moertel CG, Hahn RG, Creagan ET (1979) Toxicity and pharmacokinetics, of a pyrrolizidine alkaloid, indicine N-oxide, in humans. Cancer Res 39:4540

    Google Scholar 

  7. Kugelman M, Liu WC, Axelrod M, McBride TJ, Rao KV (1976) Indicine N-oxide: the antitumor principle of Heliotropium indicum. Lloydia (Cincinnati). 39:125

    Google Scholar 

  8. Letendre L, Smithson WA, Gilchrist GS, Burgert EO, Hoagland CH, Ames MM, Powis G, Kovach JS, (1981) Activity of indicine N-oxide in refractory acute leukemia. Cancer 47:437

    Google Scholar 

  9. Mattocks AR, Schoental R, Crowley HC, Culvenor CCJ (1961) Indicine: The major alkaloid of Helotropium indicum. LJ Chem Soc (Lond) 161:5400

    Google Scholar 

  10. McLean EK (1970) The toxic reactions of pyrrolizidine, (Senecio) alkaloids. Pharmacol Res Commun 22:429

    Google Scholar 

  11. Metzler CM, Elfring GL, McEwen AJ (1974) A package of computer programs for pharmacokinetic modeling. Biometrics 30:567

    Google Scholar 

  12. Morselli PL (ed) (1968) Drug disposition during development. Spectrum, New York, Chap. 2–6

    Google Scholar 

  13. Nichols WC, Moertel CG, Rubin J, Schutt AJ, Britell JC (1981) Phase II trial of indicine N-oxide (IND1) in patients with advanced colorectal carcinoma. Cancer Treat Rep 65:337

    Google Scholar 

  14. Rakieten N, Cooney DA, Davis RD (1974) Toxicity studies on NSC 132319, indicine N-oxide following single IV (intravenous) administration to beagle dogs. Chem Abs 81:114824

    Google Scholar 

  15. Rowland M, Tozer TN (1980) Clinical pharmacokinetics concepts and applications. Lea & Febiger, Philadelphia, p 218

    Google Scholar 

  16. Rylance G (1981) Clinical pharmacology. Br J Med 282:50

    Google Scholar 

  17. Sladek NE, Priest J, Doeden D, Microcha CJ, Pathre S, Krivit W (1980) Plasma half-life and urinary excretion of cyclophosphamide in children. Cancer Treat Rep 64:1061

    Google Scholar 

  18. Snedecor OW, Cochran WG (1968) Statistical methods, 6th edn. Iowa State University Press, Ames, pp 184, 557

    Google Scholar 

  19. Udkow G (1978) Pediatric clinical pharmacology. Am J Dis Child 132:1025

    Google Scholar 

  20. Wang Y-M, Kim P-Y, Lantin E, van Eys DL, Romsdahl MM, Sutow WW (1978) Degradation and clearance of methotrexate in children with osteosarcoma receiving high-dose infusion. Med Pediatr Onc 4:221

    Google Scholar 

  21. Wang Y-M, Sutow WW, Romsdahl MM, Perez C (1979) Age-related pharmacokinetics of high-dose methotrexate in patients with osteosarcoma. Cancer Treat Rep 63:405

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Developmental Oncology Research, Department of Oncology, Mayo Clinic, 55905, Rochester, MN

    Matthew M. Ames

  2. Department of Pediatrics, Ohio State University, 43205, Columbus, OH

    James S. Miser, Carla S. Hughes & Dianne M. Davis

  3. Columbus Childrens Hospital, 43205, Columbus, OH

    James S. Miser, Carla S. Hughes & Dianne M. Davis

  4. Department of Pediatrics, Mayo Clinic, 55905, Rochester, MN

    William A. Smithson

  5. Department of Pediatrics, Rainbow Babies and Childrens Hospital, Case Western Reserve University, 44106, Cleveland, OH, USA

    Peter F. Coccia

Authors
  1. Matthew M. Ames
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James S. Miser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William A. Smithson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter F. Coccia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Carla S. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dianne M. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ames, M.M., Miser, J.S., Smithson, W.A. et al. Pharmacokinetic study of indicine N-oxide in pediatric cancer patients. Cancer Chemother. Pharmacol. 10, 43–46 (1982). https://doi.org/10.1007/BF00257237

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00257237

Keywords

Search

Navigation