Absorption, distribution, metabolism and excretion of the P2Y12 receptor antagonist selatogrel after subcutaneous administration in healthy subjects.
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| Abstract |
The P2Y12 receptor antagonist selatogrel which exhibits rapid inhibition of platelet aggregation following subcutaneous administration is in development for the treatment of acute myocardial infarction.This human ADME study was performed in six healthy male subjects to determine the routes of elimination and to identify/quantify the metabolites of selatogrel at a therapeutically relevant dose of 16 mg [14C]-radiolabelled selatogrel.The median tmax and t1/2 of selatogrel was 0.75 h and 4.7 h, respectively. It was safe and well tolerated based on adverse event, ECG, vital sign and laboratory data.Geometric mean total recovery of [14C]-radioactivity was 94.9% of which 92.5% was recovered in faeces and 2.4% in urine.Selatogrel was the most abundant entity in each matrix. In plasma, no major metabolite was identified. In excreta, the glucuronide M21 (14.7% of radioactivity) and the mono-oxidized A1 (6.2%) were the most abundant metabolites in urine and faeces, respectively.Overall, none of the metabolic pathways contributed to a relevant extent to the overall elimination of selatogrel, i.e. by more than 25% as defined per regulatory guidance. Hence, no pharmacokinetic interaction studies with inhibitors or inducers of drug-metabolizing enzymes are warranted for clinical development of selatogrel.
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| Authors | Mike Ufer, Christine Huynh, Jan Jaap van Lier, Eva Caroff, Hartmut Fischer, Jasper Dingemanse |
| Journal | Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 50 Issue 4 Pg. 427-434 (Apr 2020) ISSN: 1366-5928 [Electronic] England |
| PMID | 31322041 (Publication Type: Journal Article) |
| Chemical References |
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