[Genotoxic effects of metabolic derivatives of the new drug phosphabenzide]. / Genotoksicheskie éffekty metabolicheskikh proizvodnykh novogo lekarstvennogo preparata fosfabenzida.

Genotoxic action of four possible metabolites of the new tranquilizer phosphabenzide (acetylphosphabenzide, diphenylphosphinylacetic acid, phosphabenzide hydrazone with pyruvic acid, bis-1,2-(diphenylphosphinylacetyl)hydrazine) has been studied. These metabolites belong to slightly toxic phosphororganic compounds. The Ames Salmonella/microsomes tests performed on strains TA100 and TA98 showed that of these compounds only acetylphosphabenzide possessed mutagenic action. Metabolic activation of liver microsomes decreased the mutagenic effect. The mechanism of action of acetylphosphabenzide is likely to involve the formation of acetylhydrazine, capable of producing active electrophiles attacking DNA.

[Determination of acetylation phenotype in the therapeutic monitoring of drugs]. / Opredelenie fenotipa atsetilirovaniia dlia terapevticheskogo monitoringa lekarstvennykh sredstv.

New methods for detecting the acetylation phenotype have been developed for therapeutic monitoring using isoniazid as the pharmacogenetic marker. The study is carried out with 4-chloro-5,7-dinitrobenzofurane by direct spectrophotometry, high performance liquid and thin-layer chromatography. The methods proved to be highly sensitive, selectively detecting isoniazid, simple, and requiring no sophisticated equipment. The methods were tried in examinations of patients with visceral diseases. Effects of various inductors on the acetylation rate were assessed.