Absorption, Distribution, Metabolism, and Excretion of [(14)C]iptacopan in Healthy Male Volunteers and in In Vivo and In Vitro Studies.
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James AD, Kulmatycki K, Poller B, Romeo AA, Van Lier JJ, Klein K, Pearson D
Absorption, Distribution, Metabolism, and Excretion of [(14)C]iptacopan in Healthy Male Volunteers and in In Vivo and In Vitro Studies.
Drug Metab Dispos. 2023 Jul;51(7):873-883. doi: 10.1124/dmd.123.001290. Epub 2023 Jun 12.
- PubMed ID
- 37308298 [ View in PubMed]
- Abstract
Iptacopan (LNP023) is an oral, small-molecule, first-in-class, highly potent proximal complement inhibitor that specifically binds factor B and inhibits the alternative complement pathway. Iptacopan is currently in development as a targeted treatment of paroxysmal nocturnal hemoglobinuria and multiple other complement-mediated diseases. In this study, the absorption, distribution, metabolism, and excretion (ADME) of iptacopan was characterized in six healthy volunteers after a single 100 mg oral dose of [(14)C]iptacopan. This was supplemented with an in vivo rat ADME study and metabolite exposure comparisons between human, rat, and dog, in addition to in vitro assays, to better understand the clearance pathways and enzymes involved in the metabolism of iptacopan. The fraction of [(14)C]iptacopan absorbed was estimated to be about 71%, with a time to maximum concentration of 1.5 hours and elimination half-life from plasma of 12.3 hours. Following a single dose of [(14)C]iptacopan, 71.5% of the radioactivity was recovered in feces and 24.8% in urine. [(14)C]iptacopan was primarily eliminated by hepatic metabolism. The main biotransformation pathways were oxidative metabolism via CYP2C8, with M2 being the major oxidative metabolite, and acyl glucuronidation via UGT1A1. The two acyl glucuronide metabolites in human plasma, M8 and M9, each accounted for
DrugBank Data that Cites this Article
- Drugs
- Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Iptacopan Alpha-1-acid glycoprotein 1 Protein Humans YesBinderDetails Iptacopan Serum albumin Protein Humans NoBinderDetails - Drug Reactions
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