Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species

• DOI: 10.1016/j.ejps.2017.03.020
• Publication Date: 2017-03-16T21:48:10Z
• Authors: Lene Jensen; Hans Helleberg; Ad Roffel; Jan Jaap van Lier; Inga Bjørnsdottir; Palle Jacob Pedersen; Everton Rowe; Julie Derving Kar...; Mette Lund Pedersen
• Keywords: Semaglutide

Semaglutide is a human glucagon-like peptide-1 analogue in clinical development for the treatment of type 2 diabetes. The absorption, metabolism and excretion single 0.5mg/450μCi [16.7MBq] subcutaneous dose [3H]-radiolabelled semaglutide was investigated healthy subjects compared with data from nonclinical studies. Radioactivity blood, plasma, urine faeces determined humans, rats monkeys; radioactivity expired air humans rats. Metabolites were quantified following profiling radiodetection. blood-to-plasma ratio pharmacokinetics both radiolabelled semaglutide-related material (in only) assessed. Intact primary component circulating plasma species, accounting 69-83% total amount material, metabolised prior to excretion. Recovery excreted 75.1% 72.1% 58.2% monkeys. Urine shown be important routes excretion, as route animals. through proteolytic cleavage peptide backbone sequential beta-oxidation fatty acid sidechain, not confined specific organs. accounted 3.1% administered less than 1% rats; it detected metabolite profiles appear similar species investigated.