Comparative pharmacokinetics of dirithromycin and erythromycin in normal volunteers with special regard to accumulation in polymorphonuclear leukocytes and in saliva
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Objective: In a randomized cross-over study, we assessed pharmacokinetics and intracellular concentrations in polymorphonuclear leukocytes (PMN) and saliva of erythromycin and erythromycylamine, the active metabolite of dirithromycin.
Methods: Ten healthy volunteers received 1 g erythromycin b.i.d. or 500 mg dirithromycin qd for 5 days (wash out period, 35 days). Concentrations of erythromycin and erythromycylamine were measured in serum, urine, saliva, and granulocytes by bioassay and high-performance liquid chromatography (HPLC) on days 1, 3, and 5 of each study period, respectively.
Results: While maximal serum concentrations (Cmax) and the area under the data (AUDtot) of erythromycin were significantly higher (Cmax 1.44 mg · l−1, AUDtot 5.66 mg · h · l−1) than those of erythromycylamine (Cmax 0.29 mg · l−1, AUDtot 1.96 mg · h · l−1), erythromycylamine had a significantly higher mean residence time (21 h) than erythromycin (5.5 h). Erythromycylamine accumulated significantly more in PMN than erythromycin;␣the accumulation factor of erythromycylamine 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 (erythromycin 0.35 mg · l−1, erythromycylamine 0.31 mg · l−1).
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