Comparative pharmacokinetics of macrolide antibiotics and concentrations achieved in polymorphonuclear leukocytes and...

OBJECTIVES: The pharmacokinetics of macrolide antibiotics --- erythromycin (ER), clarithromycin (CL), roxithromycin (RO), azithromycin (AZ), dirithromycin (DI) and the concentrations achieved in polymorphonuclear neutrophils (PMNs) and saliva were investigated. METHODS: In a four-way crossover trial, 10 healthy volunteers received 1000 mg ER twice a day, 500 mg CL twice a day, 150 mg RO twice a day and 500 mg AZ every day over a period of 3 days. In a second trial, 10 healthy volunteers received 500 mg DI every day over a period of 5 days. Concentrations of these antibiotics were measured in serum, urine, saliva and PMNs by high-performance liquid chromatography (HPLC) on days 1 and 3 in the first trial and on days 1 and 5 in the second trial. RESULTS: We found considerable differences in the pharmacokinetics, not only in serum, but also in PMNs and saliva. All substances except RO exhibited higher concentrations in PMNs than in serum, indicating excellent intraphagocytic distribution. In contrast, concentrations in saliva were lower than those measured in serum, with the exception of AZ. ER is characterized by low serum concentrations and moderate concentrations in saliva and PMNs. CL reached considerable concentrations in serum, saliva and PMNs. RO achieved the highest serum levels, but concentrations in saliva and in PMNs were below the detection limit. In contrast, AZ and DI yielded the lowest serum concentrations and the highest saliva and PMN concentrations. CONCLUSIONS: Our data emphasize the importance of tissue distribution, in addition to serum kinetics, in evaluating the pharmacokinetic profiles of antibiotics.