Tissue-directed pharmacokinetics

Abstract

Azalide antibiotics demonstrate pharmacokinetics distinct from all antibacterial agents in common use. Following oral absorption, conventional oral antibiotics diffuse through serum and interstitial compartments and are eliminated rapidly. A minimal to moderate degree of intracellular penetration may be observed. The pharmacokinetics of azithromycin, the first azalide, are characterized by a rapid and extensive movement of the drug from the serum into intracellular compartments. A dynamic equilibrium exists between the intracellular, interstitial, and serum compartments, with predominant flux into tissue sites. Azithromycin is concentrated to a high degree within phagocytes and transported by chemotactic mechanisms to the site of infection. High concentrations of azithromycin are found in pulmonary, genital, and lymphatic tissues. Azithromycin's serum levels decline in a polyphasic manner with a terminal half-life of approximately 60 hours. These kinetics allow azithromycin to be administered once daily. It is predicted that after drug administration for 5 days, therapeutic levels of azithromycin will be maintained at the tissue sites of infection for an additional 4–7 days. Consideration of the extravascular pharmacodynamics of azithromycin is necessary when making predictions regarding its therapeutic application.