title: The synthesis of [(14) C]AZD5122. Incorporation of an IV (14) C-microtracer dose into a first in human study to determine the absolute oral bioavailability of AZD5122.
abstract: AZD5122, N-(2-(2,3-difluorobenzylthio)-6-((2R,3R)-3,4-dihydroxybutan-2-ylamino)pyrimidin-4-yl)azetidine-1-sulfonamide was under investigation as a potential chemokine receptor CXCR2 antagonist for the treatment for inflammatory diseases. To gain a better understanding of the human pharmacokinetic profile, an exploratory phase I IV microtracer study was conducted using carbon-14 radiolabelled AZD5122. [(14) C]AZD5122 was carbon-14 labelled in the pyrimidine ring in five steps in an overall radiochemical yield of 19% from [(14) C]thiourea. The absolute oral bioavailability of AZD5122 was assessed in healthy subjects by an oral administration of AZD5122, followed by a concomitant intravenous [(14) C]AZD5122 microdose.
authors.affiliation: Drug Safety & Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge Science Park, Cambridgeshire, CB4 0WG, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hickey
authors.affiliation: Drug Safety & Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge Science Park, Cambridgeshire, CB4 0WG, UK.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Allen
authors.affiliation: Drug Safety & Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: Lee P
authors.initials: LP
authors.lastname: Kingston
authors.affiliation: Drug Safety & Metabolism, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge Science Park, Cambridgeshire, CB4 0WG, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilkinson
mesh_terms: D000284:Administration, Oral; D001384:Azetidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002250:Carbon Radioisotopes / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D011849:Radioactive Tracers; D013449:Sulfonamides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: C000624963:AZD5122; D001384:Azetidines; D002250:Carbon Radioisotopes; D011849:Radioactive Tracers; D013449:Sulfonamides
keywords: AZD5122; IV Microtracer; carbon-14