Comparison of the plasma, urine and blister fluid pharmacokinetics of clarithromycin and azithromycin in normal subjects

This open-label, multiple-dose study was intended to evaluate the pharmacokinetics of clarithromyin and azithromycin in plasma/serum, urine, and inflammatory and noninflammatory blister fluid, in 8 normal subjects. Co-modelling of the plasma/serum and urine data for each drug produced complex multicompartment models. Observed versus fitted drug concentration analyses evidenced a good fit of the data, despite moderate coefficient of variation values for all parameters. Blister fluid analyses demonstrated significant concentrating of both drugs in inflammatory versus noninflammatory conditions (areas under the blister fluid concentration versus time curves 31.6 versus 11.2 mg . h/L for clarithromycin and 2.88 versus 0.07 mg . h/L for azithromycin), although there was no significant difference in degree of accumulation between the agents. The results of this study are consistent with previous reports demonstrating white blood cell delivery of clarithromycin and azithromycin, and the concentrating of these agents in inflamed/infected areas.