Age and sex effects on the pharmacokinetics of linezolid

To evaluate the possible effects of age and sex on the pharmacokinetics of linezolid in healthy volunteers.

A single 600-mg dose of linezolid was administered orally to young (18-40 years) and elderly (> or =65 years) healthy males and females. Blood and urine samples were collected until 48 h after dosing and assayed for linezolid concentrations using a validated high-performance liquid chromatography method. Pharmacokinetic parameters were assessed using noncompartmental methods. Comparisons of the pharmacokinetic parameters for each age and sex group were performed using a two-way analysis of variance model. Pairwise comparisons were done using least-square means analysis.

Peak plasma drug concentrations occurred within 1.5 h after linezolid administration for males and females in both age groups. However, the maximum concentration achieved differed significantly between males and females. There was no significant difference between males and females or young and elderly for mean apparent elimination rate constant or half-life. There was no difference in mean apparent oral clearance (CLPO) between the young and elderly; however, there was a significant difference between males and females. Mean CLPO for females was approximately 37% less than mean CLPO for males when not corrected for body weight. Correcting for differences in weight reduced this difference to approximately 20%. Overall, females had a slightly lower volume of distribution than males, but this was not affected by the age of subjects.

A dose adjustment based on age and sex is not warranted due to the wide range of linezolid concentrations that are well tolerated and the relative small difference in linezolid disposition between males and females.