Metabolism study of dihydro-alpha-ergocryptine,9,10-[9,10-3H(N)] in rat and human hepatocyte cultures and rat, monkey, and human microsomes.
An in vitro approach was undertaken to investigate the metabolite profile of dihydro-alpha-ergocryptine,9,10-[9,10 ( -3 ) H(N)] in humans by comparison with two species, rat and monkey, for toxicological studies. Hepatocytes (rat and human) and microsomes (rat, monkey, and human) were used in this study, and a high-performance liquid chromatography system was developed to determine the metabolic profiles. From the two in vitro metabolizing systems it was concluded that the compound was extensively metabolized in all species, with a similar overall rate of 4.5 ng/min/mg protein in the microsomal system. The human metabolite profile in hepatocytes showed an intersubject variability that was not confirmed with microsomes. The more complex human pattern consisted of eight metabolites (based on chromatographic properties) that were produced in rats (major part) or in monkeys. Of these eight metabolites, seven were produced by rat microsomes and six by the monkey microsomes. Because of qualitative and quantitative differences, it was not possible to show that the human metabolite profile was closer to the rat's or to the monkey's. The conclusion is that all the observed metabolites in human are produced either in rats (for a major part) or in monkeys, so that these two species cover the human metabolic pattern for toxicological studies.
Mas-Chamberlin
C
C
Biotec Centre, Orleans, France.
Bromet
N
N
Olgiati
V
V
Girardello
R
R
Lowenthal
D T
DT
D000328:Adult; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004088:Dihydroergotoxine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D004088:Dihydroergotoxine