Linezolid, a novel oxazolidinone antibiotic: Assessment of monoamine oxidase inhibition using presser response to oral tyramine

The primary objective of this study was to compare the effects of oral line zolid with moclobemide and placebo on the presser response to oral tyramine . Secondary objectives were to determine possible mechanisms of the effect based on changes in the pharmacokinetics of tyramine and to evaluate altern ative methods for quantifying the presser effect. Subjects received linezol id (625 mg bid orally) moclobemide (150 mg tid orally), or placebo for up t o 7 days. Using the oral tyramine dose producing a > 30 mmHg increase in sy stolic blood pressure (SBP) (PD> 30), a positive presser response was defin ed as a PD> 30 index (pretreatment/treatment ratio of PD> 30) of greater th an or equal to 2. There were 8/10, 11/11, and 1/10 responders with linezoli d, moclobemide, and placebo, respectively Responses returned to baseline wi thin a days of drug discontinuation. The ratio of mean greatest SEP and hea rt rate at the time of greatest SEP (GSBP/HR) increased linearly with tyram ine dose both pretreatment and during treatment with linezolid and moclobem ide. During treatment, responses to tyramine when subjects took linezolid o r moclobemide were significantly different from placebo. Both drugs signifi cantly decreased tyramine oral clearance compared with placebo. Urinary exc retion of catecholamines and metabolites was consistent with MAOI activity of the drugs, but results were variable. The MAOI activity of linezolid is similar to that of moclobemide, a drug used clinically without food restric tions. Restrictions to normal dietary intake of tyramine-containing foods a re not warranted when taking linezolid. (C) 2001 the American College of Cl inical Pharmacology.