title: Effect of oral linezolid on the pressor response to intravenous tyramine.
abstract: OBJECTIVE
  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.
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. mireille.cantarini@astrazeneca.com
authors.forename: Mireille V
authors.initials: MV
authors.lastname: Cantarini
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Painter
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Gilmore
authors.forename: Catherine
authors.initials: C
authors.lastname: Bolger
authors.forename: Claire L
authors.initials: CL
authors.lastname: Watkins
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hughes
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D018592:Cross-Over Studies; D006801:Humans; D007262:Infusions, Intravenous; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D020912:Moclobemide / Q000008:administration & dosage / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000494:pharmacology; D014439:Tyramine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D008996:Monoamine Oxidase Inhibitors; D023303:Oxazolidinones; D000069349:Linezolid; D020912:Moclobemide; D014439:Tyramine