Experimental toxicology of ASTA Z 7557 (INN mafosfamide) View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1984-06

AUTHORS

Joerg Pohl, Peter Hilgard, Wolfgang Jahn, Hans-Juergen Zechel

ABSTRACT

The LD 50 of Z 7557 in mice was between 500 and 625 mg/kg after i.v. and around 2310 mg/kg after oral administration. The corresponding LD 10 was around 435 mg/kg (i.v.) or 1100-1250 mg/kg (p.o.), respectively. The LD 50 values in rats were in the range of 250-310 mg/kg after i.v. administration and around 1000-1250 mg/kg if given orally. With repeated daily i.v. injections only 70% of the daily dose contributed to lethality. A second administration of Z 7557 to rats after reversal of all toxic signs from the first administration induced the same symptoms and degree of toxicity as the initial injection. Reversible myelosuppression was the predominant feature of toxicity in mice and rats, but at equimolar doses this myelotoxicity was less than half that of cyclophosphamide (CP). First signs of immunosuppression were seen only at 100 mg/kg i.v.. No severe urotoxicity was observed in rats with single i.v. doses up to 192 mg/kg. This might be due to the fast and complete renal excretion of the thiol moiety of Z 7557, whereas the activated oxazaphosphorine component occurred in the urine only to a much smaller amount, as could be shown by a pilot pharmacokinetic study. In conclusion, Z 7557 appeared to have an overall tolerance in rats and mice similar to cyclophosphamide but was clearly less toxic with respect to the bone marrow, the immune system and the urinary tract. More... »

PAGES

201-206

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00232352

DOI

http://dx.doi.org/10.1007/bf00232352

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023463040

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/6469515


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