Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Azithromycin: Enhanced Tissue Activity and Minimal Drug Interactions

Abstract

OBJECTIVE: To review the pharmacokinetics and pharmacodynamics of oral and intravenous azithromycin compared with other macrolide antibiotics, and to evaluate these differences and their relation to clinical effectiveness. DATA SOURCE: A MEDLINE search (1966–May 1998) was performed to identify applicable English-language clinical, animal, and microbiologic studies pertaining to pharmacokinetic and pharmacodynamic parameters. STUDY SELECTION: Relevant studies concerning microbiology, pharmacokinetics, tissue concentrations, pharmacodynamics, and the clinical effects of these parameters were selected. DATA SYNTHESIS: The structural modification that distinguishes the azalide antibiotics from the macrolide antibiotics is responsible for the pharmacokinetic and pharmacodynamic behavior of azithromycin, resulting in the high and sustained tissue and intracellular concentrations seen with this agent. Drug delivery to the site of infection by phagocytes and fibroblasts is the hallmark of azithromycin's tissue-directed pharmacodynamics, allowing for convenient once-daily, 5-day regimens for most infections that respond to oral therapy and 7–10 days for more serious infections requiring initial intravenous therapy. Metabolism is via hepatic pathways other than cytochrome P450, thus minimizing the risk of drug interactions. CONCLUSIONS: Compared with other macrolide antibiotics, the unique pharmacokinetic and pharmacodynamic features of azithromycin offer the potential for improved efficacy and safety from drug interactions. These attributes, combined with its once-daily dosing schedule, make azithromycin suitable for the treatment of many types of bacterial infection.