Prevention of the mutagenic activation of an antischistosomal isothiocyanate in primates by an antibiotic.
Administration of 4 nitro-4' isothiocyano-diphenylamine (CGP 4540, amoscanate) to two nonhuman primates, Macaca mulatta and Cebus apella, resulted in the appearance of mutagenic material in the urines of these animals. Mutagenic metabolites of this drug could also be detected in the urines when the drug was administered to primates infected with Schistosoma mansoni and Schistosoma japonicum. As observed previously in mice, the mutagenic activation of amoscanate can be prevented in primates by coadministration of a single oral dose of erythromycin with no concomitant reduction in antischistosomal activity. The protective effect of erythromycin was confirmed in several crossover experiments. This dissociation of mutagenic from chemotherapeutic effects provides an opportunity to reduce serious potential long-term risks of this antischistosomal drug.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002428:Cebus; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000378:metabolism*; D004917:Erythromycin / Q000494:pharmacology*; D005260:Female; D017879:Isothiocyanates; D008253:Macaca mulatta; D008297:Male; D009153:Mutagens / Q000037:antagonists & inhibitors*; D012556:Schistosomicides / Q000494:pharmacology*; D013861:Thiocyanates / Q000378:metabolism* / Q000494:pharmacology
D000814:Aniline Compounds; D017879:Isothiocyanates; D009153:Mutagens; D012556:Schistosomicides; D013861:Thiocyanates; D004917:Erythromycin; D004159:Diphenylamine; C012391:amoscanate