Premium
Linezolid, a Novel Oxazolidinone Antibiotic: Assessment of Monoamine Oxidase Inhibition Using Pressor Response to Oral Tyramine
Author(s) -
Antal Edward J.,
Hendershot Pamela E.,
Batts Donald H.,
Sheu WangPui,
Hopkins Nancy K.,
Donaldson Kirsteen M.
Publication year - 2001
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700122010294
Subject(s) - moclobemide , tyramine , linezolid , placebo , pharmacology , medicine , pharmacodynamics , monoamine oxidase , pharmacokinetics , anesthesia , chemistry , biology , biochemistry , antidepressant , staphylococcus aureus , enzyme , genetics , alternative medicine , pathology , vancomycin , bacteria , hippocampus
The primary objective of this study was to compare the effects of oral linezolid with moclobemide and placebo on the pressor 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 alternative methods for quantifying the pressor effect. Subjects received linezolid (625 mg bid orally), moclobemide (150 mg tid orally), or placebo for up to 7 days. Using the oral tyramine dose producing a > 30 mmHg increase in systolic blood pressure (SBP) (PD >30 ), a positive pressor response was defined as a PD > 30 index (pretreatment/treatment ratio of PD > 30 ) of ≥ 2. There were 8/10, 11/11, and 1/10 responders with linezolid, moclobemide, and placebo, respectively. Responses returned to baseline within 2 days of drug discontinuation. The ratio of mean greatest SBP and heart rate at the time of greatest SBP (GSBP/HR) increased linearly with tyramine dose both pretreatment and during treatment with linezolid and moclobemide. During treatment, responses to tyramine when subjects took linezolid or moclobemide were significantly different from placebo. Both drugs significantly decreased tyramine oral clearance compared with placebo. Urinary excretion 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 restrictions. Restrictions to normal dietary intake of tyramine‐containing foods are not warranted when taking linezolid.