TABLE 3

Summary of reversibility results of binding to CYP3A by metabolism-based inhibitors obtained from the MBI reversibility assay, and previously reported information

Each datum is a mean of duplicate analyses. Each % of control datum after a 0- or 30-min preincubation followed by the incubation with (+K3Fe(CN)6) or without (–K3Fe(CN)6) potassium ferricyanide is shown below. Judgment of the reversibility was determined as described under Materials and Methods.


Inhibitor

Concentration

% of control (0 min)

% of control (30 min)

Judgment

Reported Information
-K3Fe(CN)6
+K3Fe(CN)6
-K3Fe(CN)6
+K3Fe(CN)6
μM
Diltiazem 100 85.7 92.5 62.3 90.7 Quasi-irreversible MI complex
Verapamil 10 71.5 80.1 41.2 70.1 Quasi-irreversible MI complex
Nicardipine 1 58.3 75.5 53.3 96.6 Quasi-irreversible MI complex
Amlodipine 100 68.0 72.1 49.3 73.2 Quasi-irreversible MI complex
Erythromycin 100 71.4 88.1 51.0 73.5 Quasi-irreversible MI complex
Clarithromycin 100 74.8 89.7 53.7 76.2 Quasi-irreversible MI complex
Troleandomycin 100 49.4 68.2 39.2 66.9 Quasi-irreversible MI complex
Sertraline 100 51.0 65.1 40.3 73.2 Quasi-irreversible
Clozapine 100 76.5 76.4 62.6 66.3 Irreversible Covalent binding to cellular proteins and GSH
Delavirdine 10 42.3 66.1 27.3 27.9 Irreversible Covalent binding to microsomal proteins
Mibefradil 1 32.4 41.4 24.5 24.8 Irreversible Irreversible binding
Ethynylestradiol 50 45.8 63.5 30.2 31.4 Irreversible Covalent binding to apoproteins and heme of P450
Prazosin 100 93.9 96.8 68.6 75.2 Irreversible
Bromocriptine 1 70.4 87.7 63.2 65.5 Irreversible
Bepridil 100 63.4 63.5 48.9 52.0 Irreversible
Bupivacaine 100 88.1 93.0 57.6 66.3 Irreversible
Buprenorphine
100
42.1
52.7
17.8
19.5
Irreversible