COMPARATIVE PHARMACOKINETICS OF DIRITHROMYCIN AND ERYTHROMYCIN IN NORMAL VOLUNTEERS WITH SPECIAL REGARD TO ACCUMULATION IN POLYMORPHONUCLEAR LEUKOCYTES AND IN SALIVA

Objective: In a randomized cross-over study, we assessed pharmacokinet ics and intracellular concentrations in polymorphonuclear leukocytes ( PMN) and saliva of erythromycin and erythromycylamine, the active meta bolite of dirithromycin.Methods: Tell healthy volunteers received Ig e rythromycin b.i.d. or 500 mg dirithromycin qd for 5 days (wash out per iod, 35 days). Concentrations of erythromycin and erythromycylamine we re measured in serum, urine, saliva, and granulocytes by bioassay and high-performance liquid chromatography (HPLC) on days 1, 3, and 5 of e ach study period, respectively. Results: While maximal serum concentra tions (C-max) and the area under the data (AUD(tot)) of erythromycin w ere significantly higher (C-max 1.44 mg . l(-1), AUD(tot) 5.66 mg . h . l(-1)) than those of erythromycylamine (C-max 0.29 mg . l(-1), AUD(t ot) 1.96 mg . h . l(-1)), erythromycylamine had a significantly higher mean residence lime (21 h) than erythromycin (5.5 h). Erythromycylami ne significantly more in PMN than the accumulation factor of erythromy cylamine was 100 with a maximal intracellular concentration of 13.4 mg . l(-1), whereas the maximal accumulation factor of erythromycin was 4 with a maximal intracellular concentration of 6.1 mg . l(-1). There were no significant differences in maximal saliva concentrations (eryt hromycin 0.35 mg . l(-1) erythromycylamine 0.31mg . l(-1)).