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.
Similar content being viewed by others
References
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
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
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
Culvenor CCJ (1968) Tumor inhibitory activity of pyrrolizidine alkaloids. J Pharm Sci 57:1112
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
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
Kugelman M, Liu WC, Axelrod M, McBride TJ, Rao KV (1976) Indicine N-oxide: the antitumor principle of Heliotropium indicum. Lloydia (Cincinnati). 39:125
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
Mattocks AR, Schoental R, Crowley HC, Culvenor CCJ (1961) Indicine: The major alkaloid of Helotropium indicum. LJ Chem Soc (Lond) 161:5400
McLean EK (1970) The toxic reactions of pyrrolizidine, (Senecio) alkaloids. Pharmacol Res Commun 22:429
Metzler CM, Elfring GL, McEwen AJ (1974) A package of computer programs for pharmacokinetic modeling. Biometrics 30:567
Morselli PL (ed) (1968) Drug disposition during development. Spectrum, New York, Chap. 2–6
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
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
Rowland M, Tozer TN (1980) Clinical pharmacokinetics concepts and applications. Lea & Febiger, Philadelphia, p 218
Rylance G (1981) Clinical pharmacology. Br J Med 282:50
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
Snedecor OW, Cochran WG (1968) Statistical methods, 6th edn. Iowa State University Press, Ames, pp 184, 557
Udkow G (1978) Pediatric clinical pharmacology. Am J Dis Child 132:1025
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
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
Author information
Authors and Affiliations
Rights 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
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00257237