Metabolism of doxophylline by rat liver microsomes.
The metabolic transformation of the bronchospasmolytic agent doxophylline (2-(7'-theophyllinemethyl)-1,3-dioxolane) was studied in vitro with phenobarbital-induced rat liver microsomal fraction containing the NADPH-generating system. Doxophylline was poorly metabolized as 95% of the recovered material was parent compound. The major metabolite resulted: 2'-hydroxyethyl ester of theophylline acetic acid. This was an unusual metabolite which possibly arose from dioxolane C2 enzymatic oxydation and subsequent ring opening. Theophylline was a minor metabolite. The per cent ratio of the two metabolites was 4:1; as we did not detected the presence of any compounds formed from N-demethylation, we concluded that doxophylline underwent a regiospecific metabolism on the N7 side chain.
Grosa
G
G
Franzone
J S
JS
Biglino
G
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000031:analogs & derivatives* / Q000378:metabolism
D013806:Theophylline; C019140:acefylline; C029797:doxofylline