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The combination of **spebrutinib** (CC-292) and **omeprazole** refers to a clinical regimen used primarily in pharmacokinetic studies to evaluate drug-drug interactions. Spebrutinib is an orally available, small-molecule, irreversible inhibitor of **Bruton's tyrosine kinase (BTK)**, which forms a covalent bond with the Cys481 residue in the ATP-binding pocket of the enzyme. It was developed by Avila Therapeutics (later acquired by Celgene) for the treatment of B-cell malignancies and rheumatoid arthritis. Omeprazole is a **proton pump inhibitor (PPI)** that suppresses gastric acid secretion by inhibiting the H+/K+-ATPase. Because spebrutinib exhibits pH-dependent solubility, clinical trials (such as NCT01766583) were conducted to assess how omeprazole-induced increases in gastric pH affect the absorption of spebrutinib. These studies demonstrated that co-administration with omeprazole significantly reduces the systemic exposure (Cmax and AUC) of spebrutinib, indicating that acid-reducing agents can impair its bioavailability.
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