ABT (1-Aminobenzotriazole) is a nonspecific and irreversible inhibitor of cytochrome P450 enzymes. ABT up-regulates expression of CYP2B6 and CYP3A4 potentially by activating nuclear receptor CAR. In freshly isolated human hepatocytes, ABT increased mRNA expression of CYP2B6 and CYP3A4 in a concentration-dependent manner. ABT also modulated CYP-inducing actions of CITCO and rifampin, the known inducers of CYP2B6 and CYP3A4[1]. ABT inhibit the RLS9-catalyzed N-acetylation of procainamide (IC(50) ∼ 30 μM), and no preincubation time dependence was evident. In agreement, oral ABT (100 mg/kg, 2 h predose) decreased the clearance of intravenous procainamide (45%) in rats, accompanied by a decreased N-acetylprocainamide-to-procainamide ratio in urine (0.74 versus 0.21) and plasma (area under the curve ratio 0.59 versus 0.11)[2]. The kinetic parameters of time-dependent inhibition of ABT for CYP2C9 in the absence and presence of (S)-warfarin (20 μM) were 0.0826 and 0.273 min(-1) for kinact and 3.49 and 0.157 mM for KI, respectively[3]. In vitro studies, conducted in both rat liver microsomes and rat hepatocytes, confirm that ABT is a time-dependent inhibitor of rat CYP orthologs[4]. ABT pretreatment causes long-lasting inhibition of oxidative drug metabolism without disruption of normal physiological processes[5].
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