Linezolid: Pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorphanHBr

Linezolid is a novel oxazolidinone antibiotic with mild reversible monoamin e oxidase inhibitor (MAOI) activity. The potential for interaction with ove r-the-counter(OTC) medications requires quantification. The authors present data evaluating the pharmacokinetic and pharmacodynamic responses to coadm inistration of oral linezolid with sympathomimetics (pseudoephedrine and ph enylpropanolamine) and a serotonin reuptake inhibitor (dextromethorphan). F ollowing coadministration with linezolid, minimal but statistically signifi cant increases were observed in pseudoephedrine and phenylpropanolamine pla sma concentrations; a minimal but statistically significant decrease was ob served in dextrorphan (the primary metabolite of dextromethorphan) plasma c oncentrations. Increased blood pressure (BP) was observed following the coa dministration of linezolid with either pseudoephedrine or phenylpropanolami ne; no significant effects were observed with dextromethorphan. None of the se coadministered drugs had a significant effect on linezolid pharmacokinet ics. Minimal numbers of adverse events were reported, potentiation of sympa thomimetic activity by linezolid was judged not to be clinically significan t, but patients sensitive to the effects of increased BP due to predisposin g factors should be treated cautiously. No restrictions are indicated for t he coadministration of dextromethorphan and linezolid. (C) 2001 the America n College of Clinical Pharmacology.