Disposition, metabolism and mass balance of [(14)C]apremilast following oral administration.
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Hoffmann M, Kumar G, Schafer P, Cedzik D, Capone L, Fong KL, Gu Z, Heller D, Feng H, Surapaneni S, Laskin O, Wu A
Disposition, metabolism and mass balance of [(14)C]apremilast following oral administration.
Xenobiotica. 2011 Dec;41(12):1063-75. doi: 10.3109/00498254.2011.604745. Epub 2011 Aug 23.
- PubMed ID
- 21859393 [ View in PubMed]
- Abstract
Apremilast is a novel, orally available small molecule that specifically inhibits PDE4 and thus modulates multiple pro- and anti-inflammatory mediators, and is currently under clinical development for the treatment of psoriasis and psoriatic arthritis. The pharmacokinetics and disposition of [(14)C]apremilast was investigated following a single oral dose (20 mg, 100 muCi) to healthy male subjects. Approximately 58% of the radioactive dose was excreted in urine, while faeces contained 39%. Mean C(max), AUC(0-infinity) and t(max) values for apremilast in plasma were 333 ng/mL, 1970 ng*h/mL and 1.5 h. Apremilast was extensively metabolized via multiple pathways, with unchanged drug representing 45% of the circulating radioactivity and <7% of the excreted radioactivity. The predominant metabolite was O-desmethyl apremilast glucuronide, representing 39% of plasma radioactivity and 34% of excreted radioactivity. The only other radioactive components that represented >4% of the excreted radioactivity were O-demethylated apremilast and its hydrolysis product. Additional minor circulating and excreted compounds were formed via O-demethylation, O-deethylation, N-deacetylation, hydroxylation, glucuronidation and/or hydrolysis. The major metabolites were at least 50-fold less pharmacologically active than apremilast. Metabolic clearance of apremilast was the major route of elimination, while non-enzymatic hydrolysis and excretion of unchanged drug were involved to a lesser extent.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Apremilast Cytochrome P450 3A4 Protein Humans NoSubstrateDetails - Drug Reactions
Reaction Details Details
