Effect of oral linezolid on the pressor response to intravenous tyramine

Abstract

Aims To investigate the effect of monoamine oxidase A inhibition from a single oral dose of linezolid on the pressor response to intravenous (i.v.) tyramine, using positive and negative controls to validate the methodology. Methods This placebo‐controlled, three‐period crossover study was conducted in 12 healthy male volunteers. Each volunteer received either one oral dose of moclobemide (300 mg), linezolid (600 mg), or placebo tablet followed by an i.v. tyramine pressor test until an increase in systolic blood pressure of at least 30 mmHg above baseline occurred. Each study day was separated by a 7‐day washout period. The dose of tyramine required to raise the blood pressure by 30 mmHg (TYR30) was calculated for each oral treatment by linear interpolation between log‐transformed doses of i.v. tyramine. The influence of body mass index (BMI) on TYR30 was also investigated. Results The tyramine sensitivity factor (ratio of the geometric least square mean TYR30 for placebo and active oral treatment) was 1.8 [90% confidence interval (CI) 1.6, 2.0, P < 0.0001] for linezolid and 2.1 (90% CI 1.8, 2.4, P < 0.0001) for the positive control moclobemide. BMI had a statistically significant effect on TYR30. Conclusions There was a significant difference in the pressor response to i.v. tyramine between linezolid and placebo. Moclobemide (positive control) and linezolid have a similar pressor response to i.v. tyramine. The statistically significant effect of BMI on TYR30 underlines the advantage of within‐individual comparisons of treatments in order to reduce variability and provide more accurate treatment estimates.

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Dietary Tyramine Restriction for Hospitalized Patients on Linezolid

“…Additionally, the dose of linezolid used was 625 mg, not the 600‐mg marketed dose. In the only other study involving administration of tyramine to subjects receiving linezolid, tyramine was administered intravenously 7 . Although linezolid coadministered with intravenous tyramine pressor testing demonstrated potentiation of SBP increases, tyramine pressor challenge tests are difficult to translate into clinical significance of drug–tyramine interactions.…”

“…Another study evaluated the effect of a single 600‐mg dose of linezolid, 300 mg of moclobemide, or placebo on the pressor response to intravenous tyramine in 12 healthy male volunteers (age 27‐46 years), with body mass index of 18‐31 kg/m 2 , no history of migraine or serotonin syndrome, and resting blood pressure <130/90 mm Hg at screening 7 . Tyramine doses of 1, 2, 4, 6, 8, and 10 mg were escalated until SBP increased at least 30 mm Hg.…”