The effect of combined pre-treatment on the metabolism of antipyrine in the rat.

Determination of the effect of the known enzyme-inducers phenobarbital-Na and spironolactone on the activity of the MFO was carried out. Male Wistar rats were treated either with 40 mg/kg phenobarbital-Na or 40 mg/kg spironolactone, and also in combination with 100 mg/kg of the MFO was inhibitor alpha-methyldopa. The activity of the MFO was assessed by changes in antipyrine half-life. Our results show that given alone both phenobarbital-Na and spironolactone are potent inducers of the MFO. Co-treatment with the enzyme-inhibitor alpha-methyldopa, however, led to different results in two cases: It slightly diminished the enzyme inducing effect of phenobarbital-Na, while the effect of spironolactone has completely ceased. These findings may suggest that phenobarbital-Na and spironolactone are acting on different cytochrome isoenzymes.