Kinetics and metabolism of p-tyramine during monoamine oxidase inhibition by mofegiline.

The effects of monoamine oxidase B (MAO-B) inhibition by mofegiline on the pharmacokinetics of p-tyramine and its major metabolite, p-hydroxyphenylacetic acid, were investigated in 24 healthy male volunteers. p-Tyramine doses were administered before and after a 14-day treatment period of 1, 12, or 24 mg mofegiline or placebo. Normalized p-tyramine for area under the plasma concentration-time curve after treatment were not significantly different from their respective before-treatment values for any of the dose groups. The relative bioavailability of p-tyramine after treatment was not significantly different from before treatment, although a tendency to a greater bioavailability was seen with the 12 and 24 mg doses. There were no significant differences between pharmacokinetic parameters for p-hydroxyphenylacetic acid. The data suggest that mofegiline maintains its selectivity for MAO-B in the intestine and liver at doses up to and including 24 mg. Therefore these doses would not be expected to be associated with the hypertensive crises normally associated with the "cheese effect."