Abstract
The so-called “cheese-reaction” — a hypertensive crisis during treatment with monoamine oxidase (MAO) inhibitors — is generally considered to result from ingestion of food containing high amounts of tyramine (TYR). In order to evaluate this effect in a controlled setting as close as possible to the clinical situation TYR has to be given orally. Additional information on the extent of intestinal MAO inhibition can be obtained during this test by measuring TYR kinetics. After oral doses of TYR causing systolic blood pressure increases of 30 mm Hg plasma and urine concentrations of both TYR and para-hydroxyphenylacetic acid (HPAA) were measured in 9 healthy subjects. The areas under the plasma level-time curves (AUC) as a measure of the amount of bioavailable substance in the body were calculated for TYR and HPAA considering the different TYR doses given (AUCspec). AUCspec (TYR) was 2.5fold higher during MAO inhibition, but AUCspec (HPAA) remained essentially unchanged. This means — contrary to an earlier assumption — that HPAA itself or the ratio HPAA/TYR is not a good index of the inhibition of intestinal TYR metabolism. From plasma concentrations the total clearance (Cltot/f) of TYR and from urinary excretion the TYR fraction eliminated in unchanged form (Fel) were calculated. Cltot/f after oral TYR load was significantly lowered by 48% (p < 0.0002) and Fel was enhanced by 200% (p < 0.0016) during MAO inhibition with brofaremine (100 mg/d × 15 d). Both kinetic parameters from plasma and urine were significantly correlated (n = 9, r = 0.806, p < 0.01). The mean relative bioavailability of TYR increased up to 300% during brofaremine treatment. It is concluded that the non-invasive measurement of urinary TYR excretion in addition to the oral TYR pressor test gives valuable information on the extent of gastrointestinal MAO inhibition. Plasma concentration data and analysis of HPAA are not needed.
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