PT  - JOURNAL ARTICLE
AU  - G Grosa
AU  - O Caputo
AU  - M Ceruti
AU  - G Biglino
TI  - Metabolism of 7-(1,3-thiazolidin-2-ylmethyl)theophylline by rat liver microsomes. Evidence for a monooxygenase-dependent step in 1,3-thiazolidine ring cleavage.
DP  - 1992 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 742--746
VI  - 20
IP  - 5
4099  - http://dmd.aspetjournals.org/content/20/5/742.short
4100  - http://dmd.aspetjournals.org/content/20/5/742.full
SO  - Drug Metab Dispos1992 Sep 01; 20
AB  - Metabolic transformation of the mucoregulator and bronchodilator 7-(1,3-thiazolidin-2-ylmethyl)theophylline was studied in vitro with a rat liver microsomal preparation containing a NADPH-generating system. The only metabolite observed was 7-theophyllinacetaldehyde. In contrast to previous literature pointing out the chemical nature of 2-substituted thiazolidine ring cleavage, the formation of 7-theophyllinacetaldehyde was mediated by monooxygenase-dependent oxidation. Possibly an unstable sulfoxide was the first metabolic product, rapidly converted to 7-theophyllinacetaldehyde by hydrolysis. The sulfoxidation was apparently catalyzed mainly by flavin-containing monooxygenases, as selective thermal inactivation and methymazole significantly reduced the rate of formation of the metabolite. No N7-dealkylation pathway producing theophylline was detected, indicating a high regioselectivity in in vitro metabolism, due to the nucleophilicity of the sulfur atom.