Azithromycin pharmacokinetics and penetration to lymph

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Infectious Diseases

Background:

• Azithromycin is a widely used antibiotic.
• Understanding its pharmacokinetic profile, particularly tissue penetration, is crucial for optimizing dosing regimens.
• Peripheral lymph serves as a key indicator of drug distribution into tissues.

Purpose of the Study:

• To investigate the pharmacokinetics of azithromycin in serum and peripheral human lymph.
• To determine the extent of azithromycin penetration into peripheral tissues.
• To evaluate the elimination half-life and potential for enterohepatic circulation.

Main Methods:

• A single oral dose of 1g azithromycin was administered to 14 healthy male volunteers.
• Serum and peripheral lymph samples were collected over 120 hours.
• Samples were analyzed using microbiological assay to determine drug concentrations.
• Pharmacokinetic parameters including peak concentration, AUC, and half-life were calculated.

Main Results:

• Mean peak serum concentration was 0.82 mg/l at 1.7h; mean peak lymph concentration was 0.22 mg/l at 3.1h.
• Enterohepatic circulation was suggested by a secondary, lower serum peak in 9/14 subjects.
• The mean lymph AUC was 68.1% of the serum AUC, with significant drug amounts remaining in tissues up to 120h.
• A prolonged elimination half-life was observed in both serum (44.2h) and lymph (50.8h) after 12 hours.

Conclusions:

• Azithromycin demonstrates excellent tissue penetration and a long terminal elimination half-life.
• These pharmacokinetic properties support a convenient once-daily dosing regimen for azithromycin.
• Improved patient compliance is a likely outcome of simplified dosing schedules.