Investigations on the in vitro dose-related metabolism of indomethacin in four laboratory species.
The influence of dose on the in vitro metabolism of indomethacin has been investigated in four laboratory species (rat, rabbit, guinea pig, hamster). It was found that in the rat and guinea pig the ratio of deacylated to demethylated metabolites was dependent on the substrate concentration of indomethacin, whereas in the rabbit the ratio remained constant in the dosage range investigated (1-10 mumoles). No demethylated product was found in the hamster but a high level of activity of the deacylase enzyme was observed. These findings may help to explain species-dependent toxicity.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D003640:Dealkylation; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007213:Indomethacin / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D007213:Indomethacin