Summary
Plasma levels of VM26 were assayed by HPLC in six ovarian cancer patients with normal renal and liver function who received the drugs as an initial 1-h IV infusion of 80 mg/m2 followed by a 24-h IV infusion of 120 mg/m2. These doses and infusion rates were chosen on the basis of mean VM26 clearance values found in a previous study, with the aim of reaching plasma steady-state levels of approximately 6 μg/ml in a short time.
Plasma steady-state levels of 4–10 μg/ml, close to those predicted theoretically, were in fact attained at 4–9 h during the second, slower infusion. Mean half-lives and clearance values were 8.6±1.1 h and 0.78±0.08 l/h/m2. Six percent of the VM26 dose was recovered as unchanged drug in the urines collected up to 24 h after the end of infusion. The glucuronide of VM26 aglycone (4′-demethylepipodophyllotoxin) was identified in the urine of all patients, in amounts corresponding to about 8% of the drug dose.
Similar content being viewed by others
References
Benet LZ (1972) General treatment of linear mammillary models with elimination from any compartment as used in pharmacokinetics. J Pharm Sci 61:536
Boxenbaum HG, Riegelman S, Elashoff RM (1974) Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm 2:123
Broggini M, Colombo T, D'Incalci M (1983) Activity and pharmacokinetics of VM26 in Lewis lung carcinoma-bearing mice. Cancer Treat Rep 67:555
Connors TA, Whisson ME (1966) Cure of mice bearing advanced plasma cell tumours with aniline mustard: The relationship between glucuronidase activity and tumour sensitivity. Nature 210:866
D'Incalci M, Sessa C, Farina P, Rossi C, Beer M, Cavalli F, Masera G, Mangioni C (1982) Clinical pharmacokinetics of VP16. Proc Am Assoc Cancer Res 23:131, abstract 131
D'Incalci M, Rossi C, Sessa C, Urso R, Zucchetti M, Farina P, Mangioni C (1984) Pharmacokinetics of VM26 in ovarian cancer patients. Cancer Treat Rep (in press)
Erba E, Ubezio P, Colombo T, Broggini M, Torti L, Vaghi M, D'Incalci M, Morasca L (1983) Flow-cytometric analysis of DNA distribution after VP16-213 treatment of Lewis lung carcinoma. Cancer Chemother Pharmacol 10:208
Evans WE, Sinkule JA, Crom WR, Dow L, Look AT, Rivera G (1982) Pharmacokinetics of teniposide (VM26) and etoposide (VP 16–213) in children with cancer. Cancer Chemother Pharmacol 7:147
Gibaldi M, Perrier D (1975a) Pharmacokinetics, Dekker, New York, p 50
Gibaldi M, Perrier D (1975b) Pharmacokinetics, appendix 5. Dekker, New York, p 297
Hill BT, Whelan RDH, Rupniak HT, Dennis LY, Rosholt MA (1981) A comparative assessment of the in vitro effects of drugs on cells by means of colony assays or flow microfluorimetry. Cancer Chemother Pharmacol 7:21
Issell BF (1982) The podophyllotoxin derivatives and VP-16 and VM26. Cancer Chemother Pharmacol 7:73
Jardine I, Strife RJ, Kozlowski J (1982) Synthesis, 470-MHz 1H, NMR spectra, and activity of delactonized dervatives of the anticancer drug etoposide. J Med Chem 25:1077
Krishan A, Paika K, Frei E III (1975) Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM-26, VP-16-213) on the cell cycle traverse of human lymphoblasts. J Cell Biol 66:521
Loike JD (1982) VP16-213 and podophyllotoxin. A study on the relationship between chemical structure and biological activity. Cancer Chemother Pharmacol 7:103
Loike JD, Brewer CF, Sternlicht H, Gensler WJ, Horwitz SB (1978) Structure-activity study of the inhibition of microtube assembly in vitro by podophyllotoxin and its congeners. Cancer Res 38:2688
Rozenczweig H, Von Hoff DD, Henney JE, Muggia F (1977) VM 26 and VP 16-213: A comparative analysis. Cancer 40:334
Sacchi-Landriani G, Guardabasso V, Rocchetti M (1983) NL-FIT: A micro-computer program for non-linear fitting. Comput Programs Biomed 16:35
Stähelin H (1970) 4-Demethyl-epipodophyllotoxin thenylidene glucoside (VM26), a podophyllum compound with a new mechanism of action. Eur J Cancer 6:303
Venditti JM (1971) Treatment schedule dependency of experimentally active antileukemic (L1210) drugs. Cancer Chemother Rep [3] 2:35
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rossi, C., Zucchetti, M., Sessa, C. et al. Pharmacokinetic study of VM26 given as a prolonged IV infusion to ovarian cancer patients. Cancer Chemother. Pharmacol. 13, 211–214 (1984). https://doi.org/10.1007/BF00269031
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00269031