Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats

M. Verschraagen, E. Boven, E. Torun, C. A M Erkelens, F. H. Hausheer, W. J F Van Der Vijgh

Research output: Contribution to journalArticle

Abstract

In preclinical studies, BNP7787 (disodium 2,2′-dithio-bis-ethane sulphonate), the disulphide form of mesna, has demonstrated selective protection against cisplatin-induced nephrotoxicity due to conversion into mesna inactivating toxic platinum species. Mesna (sodium 2-mercapto ethane sulphonate), however, can affect the antitumour activity of cisplatin, while BNP7787 does not interfere with the antitumour activity. To understand the difference in interference with cisplatin-induced antitumour activity between BNP7787 and mesna as well to characterise the selective nephroprotection by BNP7787, the pharmacokinetics of BNP7787 and mesna, each given i.v. 1000 mgkg-1, were determined in plasma, kidney, liver, red blood cells (RBC), skeletal muscle and tumour of Fischer rats bearing subcutaneously implanted WARD colon tumours. The following results were obtained: (1) high concentrations of BNP7787 and mesna were observed in the plasma and kidney after administration of BNP7787 or mesna, except for mesna in plasma after BNP7787 administration; (2) in all other sampled compartments, the AUC values of both compounds were at least 5.5-fold lower than the corresponding values in kidney; (3) the AUC of mesna in plasma after mesna administration was comparable to the AUC of mesna in kidney after a dose of BNP7787 that can completely prevent cisplatin-induced nephrotoxicity in rats; (4) the AUC of mesna in plasma was five-fold higher relative to the AUC of mesna following BNP7787 administration (P

Original languageEnglish (US)
Pages (from-to)1654-1659
Number of pages6
JournalBritish Journal of Cancer
Volume90
Issue number8
DOIs
StatePublished - Apr 19 2004
Externally publishedYes

Fingerprint

Mesna
Pharmacokinetics
Injections
Area Under Curve
Cisplatin
Kidney
2,2'-dithiodiethanesulfonic acid
Poisons
Inbred F344 Rats
Platinum
Disulfides

Keywords

  • BNP7787
  • Kidney
  • Mesna
  • Pharmacokinetics
  • Plasma
  • Tumour

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Verschraagen, M., Boven, E., Torun, E., Erkelens, C. A. M., Hausheer, F. H., & Van Der Vijgh, W. J. F. (2004). Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats. British Journal of Cancer, 90(8), 1654-1659. https://doi.org/10.1038/sj.bjc.6601719

Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats. / Verschraagen, M.; Boven, E.; Torun, E.; Erkelens, C. A M; Hausheer, F. H.; Van Der Vijgh, W. J F.

In: British Journal of Cancer, Vol. 90, No. 8, 19.04.2004, p. 1654-1659.

Research output: Contribution to journalArticle

Verschraagen, M, Boven, E, Torun, E, Erkelens, CAM, Hausheer, FH & Van Der Vijgh, WJF 2004, 'Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats', British Journal of Cancer, vol. 90, no. 8, pp. 1654-1659. https://doi.org/10.1038/sj.bjc.6601719
Verschraagen M, Boven E, Torun E, Erkelens CAM, Hausheer FH, Van Der Vijgh WJF. Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats. British Journal of Cancer. 2004 Apr 19;90(8):1654-1659. https://doi.org/10.1038/sj.bjc.6601719
Verschraagen, M. ; Boven, E. ; Torun, E. ; Erkelens, C. A M ; Hausheer, F. H. ; Van Der Vijgh, W. J F. / Pharmacokinetic behaviour of the chemoprotectants BNP7787 and mesna after an i.v. bolus injection in rats. In: British Journal of Cancer. 2004 ; Vol. 90, No. 8. pp. 1654-1659.
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