Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr

• Published in: Journal of clinical pharmacology 2001-05, Vol.41 (5), p.563
• Main Authors: Hendershot, P E, Antal, E J, Welshman, I R, Batts, D H, Hopkins, N K
• Format: Article
• Language: English
• Subjects: Acetamides - administration & dosage; Acetamides - adverse effects; Acetamides - blood; Adult; Area Under Curve; Blood Pressure - drug effects; Body Temperature - drug effects; Dextromethorphan - administration & dosage; Dextromethorphan - adverse effects; Dextromethorphan - blood; Dizziness - chemically induced; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Ephedrine - administration & dosage; Ephedrine - adverse effects; Ephedrine - blood; Female; Headache - chemically induced; Heart Rate - drug effects; Humans; Linezolid; Male; Mental Processes - drug effects; Middle Aged; Monoamine Oxidase Inhibitors - administration & dosage; Monoamine Oxidase Inhibitors - adverse effects; Monoamine Oxidase Inhibitors - blood; Nonprescription Drugs - pharmacology; Oxazolidinones - administration & dosage; Oxazolidinones - adverse effects; Oxazolidinones - blood; Phenylpropanolamine - administration & dosage; Phenylpropanolamine - adverse effects; Phenylpropanolamine - blood; Regression Analysis; Sympathomimetics - administration & dosage; Sympathomimetics - adverse effects; Sympathomimetics - blood
• ISSN: 0091-2700; 1552-4604

Linezolid is a novel oxazolidinone antibiotic with mild reversible monoamine oxidase inhibitor (MAOI) activity. The potential for interaction with over-the-counter (OTC) medications requires quantification. The authors present data evaluating the pharmacokinetic and pharmacodynamic responses to coadministration of oral linezolid with sympathomimetics (pseudoephedrine and phenylpropanolamine) and a serotonin reuptake inhibitor (dextromethorphan). Following coadministration with linezolid, minimal but statistically significant increases were observed in pseudoephedrine and phenylpropanolamine plasma concentrations; a minimal but statistically significant decrease was observed in dextrorphan (the primary metabolite of dextromethorphan) plasma concentrations. Increased blood pressure (BP) was observed following the coadministration of linezolid with either pseudoephedrine or phenylpropanolamine; no significant effects were observed with dextromethorphan. None of these coadministered drugs had a significant effect on linezolid pharmacokinetics. Minimal numbers of adverse events were reported. Potentiation of sympathomimetic activity by linezolid was judged not to be clinically significant, but patients sensitive to the effects of increased BP due to predisposing factors should be treated cautiously. No restrictions are indicated for the coadministration of dextromethorphan and linezolid.