Metabolic acetal splitting of budesonide. A novel inactivation pathway for topical glucocorticoids
- PMID: 2886320
Item in Clipboard
Metabolic acetal splitting of budesonide. A novel inactivation pathway for topical glucocorticoids
Drug Metab Dispos.
1987 May-Jun.
Abstract
Topical glucocorticoids usually have a high intrinsic glucocorticoid potency and may, after systemic uptake, induce side effects. The systemic inactivation of budesonide is rapid due to extensive liver biotransformation. The major metabolic pathway, 16 alpha, 17 alpha-acetal splitting, is unique for budesonide within this group of compounds. This biotransformation is catalyzed by microsomal monooxygenases and proceeds via hydroxylation and subsequent rearrangement to an intermediary ester. The ester is cleaved by hydrolysis to 16 alpha-hydroxyprednisolone and butyric acid. The hydrolysis product 16 alpha-hydroxyprednisolone has strongly reduced glucocorticoid activity.
Similar articles
-
Development of glucocorticosteroids with enhanced ratio between topical and systemic effects.Acta Derm Venereol Suppl (Stockh). 1989;151:11-9; discussion 47-52. Acta Derm Venereol Suppl (Stockh). 1989. PMID: 2624062
-
Metabolic pathways of the topical glucocorticoid budesonide in man.Drug Metab Dispos. 1983 Nov-Dec;11(6):590-6. Drug Metab Dispos. 1983. PMID: 6140145
-
Prospects for future topical glucocorticoid development.Acta Derm Venereol Suppl (Stockh). 1989;151:37-46; discussion 47-52. Acta Derm Venereol Suppl (Stockh). 1989. PMID: 2624065
-
Influence of 16 alpha, 17 alpha-acetal substitution and steroid nucleus fluorination on the topical to systemic activity ratio of glucocorticoids.J Steroid Biochem. 1982 Jun;16(6):779-86. doi: 10.1016/0022-4731(82)90035-8. J Steroid Biochem. 1982. PMID: 7109581
-
Review article: older systemic and newer topical glucocorticosteroids and the gastrointestinal tract.Aliment Pharmacol Ther. 1996 Aug;10(4):487-96. doi: 10.1046/j.1365-2036.1996.41183000.x. Aliment Pharmacol Ther. 1996. PMID: 8853752 Review.
Cited by
-
Benefit:Risk Profile of Budesonide in Obstructive Airways Disease.Drugs. 2019 Nov;79(16):1757-1775. doi: 10.1007/s40265-019-01198-7. Drugs. 2019. PMID: 31549299 Free PMC article. Review.
-
Metabolic pathways of inhaled glucocorticoids by the CYP3A enzymes.Drug Metab Dispos. 2013 Feb;41(2):379-89. doi: 10.1124/dmd.112.046318. Epub 2012 Nov 9. Drug Metab Dispos. 2013. PMID: 23143891 Free PMC article.