Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1987 Oct;56(4):479–483. doi: 10.1038/bjc.1987.228

Pharmacokinetics of ethylenediaminemalonatoplatinum(II) (JM-40) during phase I trial.

F Elferink 1, W J van der Vijgh 1, W W ten Bokkel Huinink 1, J B Vermorken 1, I Klein 1, B Winograd 1, M K Knobf 1, G Simonetti 1, H E Gall 1, J G McVie 1, et al.
PMCID: PMC2001825  PMID: 3689665

Abstract

Pharmacokinetics of the cis-platin analog ethylenediaminemalonatoplatinum(II) (JM-410) was studied in 28 cycles of 19 patients during the phase I study of this drug. The drug was administered intravenously by short-term (10-60 min) infusion. Doses ranged from 20 to 1,200mg m-2. JM-40 was determined in plasma ultrafiltrate and urine by HPLC. Platinum (Pt) concentrations were determined in plasma, plasma ultrafiltrate, urine and red blood cells by atomic absorption spectrometry up to 5 days after administration of the drug. Ultrafilterable Pt could be determined up to 45 days after the infusion in one patient sampled over such a long period. Pharmacokinetics of JM-40 showed a linear behaviour. The final half-life of total Pt in plasma was 4.1 +/- 0.9 days. The disposition of JM-40 was similar to that of ultrafilterable Pt in respect to t1/2 alpha (10 and 13 min), t1/2 beta (44 and 57 min), volumes of distribution Vc (11 and 121) and Vss (17 and 201), systemic clearance (256 and 223 ml min-1), renal clearance (69 and 73 ml min-1) and metabolic clearance (183 and 154 ml min-1). During the first 6 h 27 +/- 9% of the administered dose was excreted as JM-40. Cumulative platinum excretion in the urine amounted to 29 +/- 13% and 60 +/- 13% over the first 6 h, 24 h and 5 days, respectively. The uptake of platinum in red blood cells was limited, comprising only 0.24 +/- 0.12% of the administered dose. Although JM-40 and carboplatin are structurally closely related, pharmocokinetics and toxicity of JM-40 were more similar to cis-platin than to carboplatin.

Full text

PDF
479

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benet L. Z., Galeazzi R. L. Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci. 1979 Aug;68(8):1071–1074. doi: 10.1002/jps.2600680845. [DOI] [PubMed] [Google Scholar]
  2. Boven E., van der Vijgh W. J., Nauta M. M., Schlüper H. M., Pinedo H. M. Comparative activity and distribution studies of five platinum analogues in nude mice bearing human ovarian carcinoma xenografts. Cancer Res. 1985 Jan;45(1):86–90. [PubMed] [Google Scholar]
  3. Collier P. S. Some considerations on the estimation of steady state apparent volume of distribution and the relationships between volume terms. J Pharmacokinet Biopharm. 1983 Feb;11(1):93–105. doi: 10.1007/BF01061770. [DOI] [PubMed] [Google Scholar]
  4. Collins J. M., Zaharko D. S., Dedrick R. L., Chabner B. A. Potential roles for preclinical pharmacology in phase I clinical trials. Cancer Treat Rep. 1986 Jan;70(1):73–80. [PubMed] [Google Scholar]
  5. Cutbush S. D., Kuroda R., Neidle S., Robins A. B. The antitumor complex ethylenediamine platinum (II) malonate: x-ray structure analysis, and studies of its stability in solution. J Inorg Biochem. 1983 Jun;18(3):213–220. doi: 10.1016/0162-0134(83)85003-x. [DOI] [PubMed] [Google Scholar]
  6. Harland S. J., Newell D. R., Siddik Z. H., Chadwick R., Calvert A. H., Harrap K. R. Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function. Cancer Res. 1984 Apr;44(4):1693–1697. [PubMed] [Google Scholar]
  7. Joss R. A., Kaplan S., Goldhirsch A., Sessa C., Brunner K. W., Cavalli F. A phase I trial of cis-diammine-1,1-cyclobutane dicarboxylate platinum II (Carboplatin, CBDCA, JM-8) with a single dose every five week-schedule. Invest New Drugs. 1984;2(3):297–304. doi: 10.1007/BF00175380. [DOI] [PubMed] [Google Scholar]
  8. King F. G., Dedrick R. L., Farris F. F. Physiological pharmacokinetic modeling of cis-dichlorodiammineplatinum(II) (DDP) in several species. J Pharmacokinet Biopharm. 1986 Apr;14(2):131–155. doi: 10.1007/BF01065258. [DOI] [PubMed] [Google Scholar]
  9. Lelieveld P., Van der Vijgh W. J., Veldhuizen R. W., Van Velzen D., Van Putten L. M., Atassi G., Danguy A. Preclinical studies on toxicity, antitumour activity and pharmacokinetics of cisplatin and three recently developed derivatives. Eur J Cancer Clin Oncol. 1984 Aug;20(8):1087–1104. doi: 10.1016/0277-5379(84)90112-3. [DOI] [PubMed] [Google Scholar]
  10. Long D. F., Patton T. F., Repta A. J. Platinum levels in human erythrocytes following intravenous administration of cisplatin: importance of erythrocytes as a distribution site for platinum species. Biopharm Drug Dispos. 1981 Apr-Jun;2(2):137–146. doi: 10.1002/bdd.2510020206. [DOI] [PubMed] [Google Scholar]
  11. Reece P. A., Stafford I., Russell J., Gill P. G. Reduced ability to clear ultrafilterable platinum with repeated courses of cisplatin. J Clin Oncol. 1986 Sep;4(9):1392–1398. doi: 10.1200/JCO.1986.4.9.1392. [DOI] [PubMed] [Google Scholar]
  12. Vermorken J. B., van der Vijgh W. J., Klein I., Gall H. E., van Groeningen C. J., Hart G. A., Pinedo H. M. Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin. Clin Pharmacol Ther. 1986 Feb;39(2):136–144. doi: 10.1038/clpt.1986.24. [DOI] [PubMed] [Google Scholar]
  13. Vermorken J. B., van der Vijgh W. J., Klein I., Hart A. A., Gall H. E., Pinedo H. M. Pharmacokinetics of free and total platinum species after short-term infusion of cisplatin. Cancer Treat Rep. 1984 Mar;68(3):505–513. [PubMed] [Google Scholar]
  14. Wagner J. G. Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data. J Pharmacokinet Biopharm. 1976 Oct;4(5):443–467. doi: 10.1007/BF01062831. [DOI] [PubMed] [Google Scholar]
  15. Wagner J. G. Pharmacokinetic data. Pharmacokinetic parameters estimated from intravenous data by uniform methods and some of their uses. J Pharmacokinet Biopharm. 1977 Apr;5(2):161–182. doi: 10.1007/BF01066219. [DOI] [PubMed] [Google Scholar]
  16. Winograd B., Vermorken J. B., ten Bokkel Huinink W. W., Simonetti G., Gall H. E., Knobf M. K., van der Vijgh W. J., McVie J. G., Pinedo H. M. Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue. Cancer Res. 1986 Apr;46(4 Pt 2):2148–2151. [PubMed] [Google Scholar]
  17. van der Vijgh W. J., Elferink F., Postma G. J., Vermorken J. B., Pinedo H. M. Determination of ethylenediamineplatinum(II) malonate in infusion fluids, human plasma and urine by high-performance liquid chromatography. J Chromatogr. 1984 Oct 12;310(2):335–342. doi: 10.1016/0378-4347(84)80098-5. [DOI] [PubMed] [Google Scholar]
  18. van der Vijgh W. J., Klein I. Protein binding of five platinum compounds. Comparison of two ultrafiltration systems. Cancer Chemother Pharmacol. 1986;18(2):129–132. doi: 10.1007/BF00262281. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES