The metabolic profile of azimilide in man: in vivo and in vitro evaluations.
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Riley P, Figary PC, Entwisle JR, Roe AL, Thompson GA, Ohashi R, Ohashi N, Moorehead TJ
The metabolic profile of azimilide in man: in vivo and in vitro evaluations.
J Pharm Sci. 2005 Sep;94(9):2084-95.
- PubMed ID
- 16052551 [ View in PubMed]
- Abstract
The metabolic fate of azimilide in man is unusual as it undergoes a cleavage in vivo resulting in the formation of two classes of structurally distinct metabolites. During a metabolite profiling study conducted in human volunteers to assess the contribution of all pathways to the clearance of (14)C-azimilide, greater than 82% of radioactivity was recovered in urine (49%-58%) and feces (33%). Urine, feces, and plasma were profiled for metabolites. A cleaved metabolite, 4-chloro-2-phenyl furoic acid was present at high concentration in plasma (metabolite/parent AUC ratio approx. 4), while other plasma metabolites, azimilide N-oxide (metabolite/parent AUC ratio 0.001), and a cleaved hydantoin metabolite (metabolite/parent AUC ratio = 0.3) were present at lower concentrations than azimilide. In urine, the cleaved metabolites were the major metabolites, (> 35% of the dose) along with phenols (as conjugates, 7%-8%), azimilide N-oxide (4%-10%), a butanoic acid metabolite (2%-3%), and desmethyl azimilide (2%). A limited investigation of fecal metabolites indicated that azimilide (3%-5%), desmethyl azimilide (1%-3%), and the butanoic acid metabolite (< 1%) were present. Contributing pathways for metabolism of azimilide, identified through in vitro and in-vivo studies, were CYPs 1A1 (est. 28%), 3A4/5 (est. 20%), 2D6 (< 1%), FMO (est. 14%), and cleavage (35%). Enzyme(s) involved in the cleavage of azimilide were not identified.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Azimilide Cytochrome P450 1A1 Protein Humans UnknownSubstrateDetails Azimilide Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails Azimilide Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Azimilide Cytochrome P450 3A5 Protein Humans UnknownSubstrateDetails