Azithromycin levels in plasma and gastric tissue, juice and mucus

Abstract

Azithromycin is the first member of a new class called the azalides. Its distribution in gastric tissues was studied in 27 patients (mean age 66 years) with proven gastric cancer due to be resected. Five groups of patients received a single 500 mg oral dose of azithromycin 24, 48, 72, 96 or 120 h pre-operatively. Samples of blood, gastric juice, mucus and gastric tissue were taken and azithromycin assayed by high performance liquid chromatography. There was an increase in the level of azithromycin in gastric juice up to the 73-96 h period reaching a median peak of 0.20 micrograms/ml. There were higher levels of azithromycin in gastric mucus (approximately double the maximum attained in gastric juice) at each of the time periods to 120 h after the dose of azithromycin. Much higher levels were seen in the gastric tissue (median peak of 4.6 micrograms/g), which were statistically significant compared with gastric juice for the first two time periods (24-48 h, p = 0.005; 49-72 h, p = 0.012). Concentrations seen in the gastric tissue specimens were between five- and 10-fold greater than those seen in gastric mucus, and approximately 20-fold greater than the levels seen in gastric juice at each of the time periods after dosing. It is concluded that remarkably high levels of azithromycin are found in gastric tissue within 24 h of a 500 mg oral dose and that these levels persist over a five-day period. There exists a significant concentration gradient from gastric tissue to gastric juice. Such levels may be advantageous in the therapy of Helicobacter pylori infections.