[Mutagenic activity analysis of body fluids in the first phase of clinical drug trials].
On the example of the model drugs metronidazole and ornidazole, a possible use of an analysis of mutagenic activity of blood and urine in the first stage of clinical testing of drugs is demonstrated. Mutagenicity of blood and urine after metronidazole administration in the dose of 1 and 2 g was examined in 3 experiments with 6 volunteers, the presence of mutagenic drugs in urine in the dose of 1 g was observed till 48 h, in the dose of 2 g till 72 h after administration. Besides base-substitution mutations also frameschif mutations were detected, but with considerable individual variability. Mutagenic activity in blood and urine after the administration of 1 g of ornidazole was investigated in the 1st experiment in 3, in further two experiments in 8 volunteers. It was characterized by a two-peak increase in mutagenicity in blood and urine in the intervals of 1-6 h and 48-72 h. Saturation of 1 g of ascorbic acid daily in the course of 1 week prior to the administration of ornidazole was manifested by a decrease in mutagenic activity in blood and increased excretion of mutagenic drugs in urine.
Cerná
M
M
Institut pro dalsí vzdĕlávání lékarů a farmaceutů, Praha.
Dobiás
L
L
Hájek
V
V
Rössner
P
P
Srám
R J
RJ
D000328:Adult; D001769:Blood; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods*; D014556:Urine
D008795:Metronidazole
Vyuzití analýzy mutagenní aktivity tĕlních tekutin pri první fázi klinického zkousení léků.