TABLE 1

Effects of TAO, ketoconazole, and cimetidine on the metabolism of M25 in rat liver microsomes

Microsomes (0.3 mg/ml, n = 2 or 3) suspended in 0.1 M potassium phosphate buffer, pH 7.4, with 1 mM EDTA and 5 mM MgCl2 were first preincubated for 30 min with TAO and an NADPH-regenerating system. At the end of 30 min, M25 was added, and the reaction was continued for an additional 30 min. Acetonitrile-quenched reaction mixtures were analyzed by reverse-phase HPLC for the formation of M16.

Inhibitor
Conc.
Percentage of Control of Formationa
M16
μM
TAO 100 75
Ketoconazole 1 85
5 55
Cimetidine 25 —b
50 —b
100
37

  • ↵ a Percentage of control of formation of M16 was calculated relative to incubations in the absence of inhibitors.

  • ↵ b —, no inhibition detected.