Effect of gastric bypass surgery on azithromycin oral bioavailability

Abstract

Objectives: Azithromycin is used widely for community-acquired infections. The timely administration of azithromycin in adequate doses minimizes treatment failure. Gastric bypass, a procedure that circumvents the upper gut, may compromise azithromycin plasma levels. We hypothesized that azithromycin concentrations would be reduced following gastric bypass. Methods: A single-dose pharmacokinetic study in 14 female post-gastric bypass patients and 14 sex- and body mass index (BMI)-matched controls (mean age 44 years and BMI 36.4 kg/m. 2) was performed. Subjects were administered two 250 mg azithromycin tablets at time 0 and plasma azithromycin levels were sampled at 0.5, 1, 1.5, 2, 3, 5, 7 and 24 h. The AUC of the plasma azithromycin concentrations from time 0 to 24 h (AUC. 0-24) was the primary outcome. Results: Azithromycin concentrations were lower in gastric bypass patients compared with controls throughout the entire duration of sampling. Compared with controls, the AUC0-24 was reduced in gastric bypass subjects by 32% [1.41 (SD 0.51) versus 2.07 (0.75) mg h/L; P = 0.008], and dose-normalized AUC0-24 was reduced by 33% [0.27 (0.12) versus 0.40 (0.13) kg h/L; P = 0.009]. Peak azithromycin concentrations were 0.260 (0.115) in bypass subjects versus 0.363 (0.200) mg/L in controls (P = 0.08), and were reached at 2.14 (0.99) h in gastric bypass subjects and 2.36 (1.17) h in controls (P = 0.75). Conclusions: Azithromycin AUC was reduced by one-third in gastric bypass subjects compared with controls. The potential for early treatment failure exists, and dose modification and/or closer clinical monitoring of gastric bypass patients receiving azithromycin should be considered. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.