Summary
The clinical pharmacokinetics of VM26 and VP16-213 were assessed in 15 children (median age 10 years) with acute leukemia, using a new high-performance liquid chromatography—electrochemical assay. Pharmacokinetic parameters were calculated by both model-dependent and compartment model-independent methods. These studies demonstrated substantial differences in the central volumes of distribution (VDc), steady-state volumes of distribution (VDss) and systemic clearances (Cls) of VM26 and VP16-213; with the VDc, VDss, and Cls all being smaller for VM26. Systemic clearances determined by model-independent methods were 5.2±1.0 ml/min/m2 (mean±SD) for VM26 and 17.8±11.2 ml/min/m2 for VP16-213. The major metabolites detected in serum and urine were the hydroxy acids. Low levels of the picro-lactone isomers were detected in some patients while the aglycones were not detected in the serum or urine of any patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allen LM and Creaven PJ (1975) Comparison of the human pharmacokinetics of VM26 and VP16-213, two antineoplastic epipodophyllotoxin glycopyranoside derivatives. Eur J Cancer 11:697
Allen LN, Marks C, Creaven PJ (1976) 4′-demethylepipodophyllic acid-9-(4,6-0-ethylidene-β-d-glucopyranoside), the major urinary metabolite of VP16-213 in man. Proc Am Assoc Cancer Res 17:6
Brewer CF, Loike JD, Horwitz SB, Sternlicht H and Gensler WJ (1979) Conformational analysis of podophyllotoxin and its congeners, structure-activity relationship in microtubular assembly. J Med Chem 22:215
Dow L (1980) Sensitivity of normal and neoplastic cells to chemotherapeutic agents in vitro. Adv Int Med 25:427
Gensler WJ, Murthy CD and Trammell MH (1977) Nonenolizable podophyllotoxin derivatives. J Med Chem 20:635
Gibaldi M, Perrier D (1975) Multicompartment models. In: Drugs and the Pharmaceutical Sciences, vol 1. Pharmacokinetics. Marcel Dekker, Inc., New York, NY, pp 45–96
Hayes A, Green AA, Casper J, Cornet J, Evans WE (1981) Clinical evaluations of sequentially scheduled cisplatin and VM26 in neuroblastoma, Response and toxicity. Cancer 48:1715–1718
Kelly MG, Hartwell JL (1954) Podophyllotoxin: A review. J Natl Cancer Inst 14:967
Loo JCK, Riegelman S (1970) Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i.v. infusion. J Pharmacol Sci 59:53
Metzler CM, Elfring GL, and McEwen AV (1974) A package of computer programs for pharmacokinetic modeling. Biometrics 30:562
Rivera G, Aur J, Dahl GV, Pratt CB, Wood A, Avery T (1980) Combined VM26 and cytosine arabinoside in treatment of refractory childhood lymphocytic leukemia. Cancer 46:1284
Sinkule JA, Rivera G, Evans WE Clinical pharmacokinetics of VM26 (Teniposide) in children with acute lymphocytic leukemia. Proceedings, American College Clin Pharmacol, May 1981, Philadelphia, PA
Strife RJ, Jardine I and Colvin M (1980) Analysis of the Anticancer Drugs VP16-213 and VM26 and their metabolites by high-performance liquid chromatography. J Chromatogr 182:211
Yeh KC, Kwan KC (1978) A comparison of numerical integrating algorithms by Trapezoidal, Langrange, and Spline approximations. J Pharmacokinet Biopharm 6:79
Author information
Authors and Affiliations
Additional information
Supported in part by Leukemia Program Project Grant CA20180, by Cancer Center CORE Grant CA21765 and by ALSAC
Rights and permissions
About this article
Cite this article
Evans, W.E., Sinkule, J.A., Crom, W.R. et al. Pharmacokinetics of teniposide (VM26) and etoposide (VP16-213) in children with cancer. Cancer Chemother. Pharmacol. 7, 147–150 (1982). https://doi.org/10.1007/BF00254537
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00254537