title: Effect of gastric bypass surgery on azithromycin oral bioavailability.
abstract: OBJECTIVE
  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 AUC(0-24) 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 AUC(0-24) 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.
authors.affiliation: Department of Medicine,  University of Alberta, Edmonton, Alberta,  Canada.
authors.forename: Raj S
authors.initials: RS
authors.lastname: Padwal
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ben-Eltriki
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.forename: Lee-Ann
authors.initials: LA
authors.lastname: Langkaas
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
authors.forename: Dan W
authors.initials: DW
authors.lastname: Birch
authors.forename: Shahzeer
authors.initials: S
authors.lastname: Karmali
authors.forename: Dion R
authors.initials: DR
authors.lastname: Brocks
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin