Category: pharmacological
Aliases: Imbruvica, PCI-32765
First-in-class covalent BTK (Bruton tyrosine kinase) inhibitor — irreversible Michael acceptor that binds Cys481 in the BTK ATP pocket. Indications: CLL/SLL, mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, cGVHD. Strong CYP3A4 substrate (F ~3%; raising it to ~10% with mild inducers, contraindicated with strong inhibitors due to risk of atrial fibrillation + bleeding). Off-target effects on EGFR, ITK, TEC, HER2 account for the rash + diarrhea + AF profile. PK (Imbruvica label, SS 560 mg PO qd): AUC 953 ± 705 ng·h/mL, t½ 4-6 h, Tmax 1-2 h, absolute F 2.9% fasted (doubles to ~6% with food — administration with food recommended). Apparent V/F ~4200 L; true Vd ~122 L. CYP3A4 substrate; massive food effect + strong inducer/inhibitor sensitivity.
PO: 5h