Absorption of Drugs Post-Bariatric Surgery (Absorb-Azithromycin)
Condition: Bariatric Surgery
Study type: Interventional

Summary: 
      Bariatric (obesity) surgery has become the preferred treatment option for patients with
      severe obesity and is increasing in popularity. It is commonly performed, with nearly 350 000
      operations in the world every year. The most common type of bariatric surgery is gastric
      bypass, in which stomach size is reduced by 95% and the upper intestine is bypassed. Bypass
      of the upper intestine may lead to medication malabsorption, although this potential adverse
      effect has received little study.

      The objective of this study is to determine whether gastric bypass reduces the absorption of
      a azithromycin, a medication commonly prescribed first-line for infections, especially
      pneumonia. Patients and non-surgical controls will receive a single dose of azithromycin
      under highly standardized study conditions. The absorption of azithromycin will be calculated
      and compared between surgical and non-surgical study groups.

      The investigators hypothesis is that there will be a significant reduction in the absorption
      of azithromycin in gastric bypass patients compared to non-surgical controls. This raises the
      possibility that post-gastric bypass patients treated with azithromycin may fail to respond
      to treatment, become worse and even die. This study will have important implications for the
      large number of past and future gastric bypass recipients.
    

Detailed description: 
      In the past decade, bariatric surgery has emerged as the preferred treatment option for
      patients with either severe obesity [body mass index (BMI) ≥ 40 kg/m2] or moderate obesity
      (BMI 35.0-39.9 kg/m2) and a major medical complication (e.g., diabetes, hypertension, sleep
      apnea). Surgery reduces weight by 33% after 2-3 years, and is associated with improvements in
      obesity-related comorbidities, mortality and quality of life.

      Consequently, demand for bariatric surgery is increasing at an exponential rate in Canada,
      the United States and globally, with 350 000 estimated surgeries performed annually globally.
      Laparoscopic Roux-en-Y gastric bypass is the most commonly performed type of bariatric
      procedure. This operation restricts stomach capacity 5% of its original size and bypasses the
      duodenum and much of the jejunum. The major adverse consequence of intestinal bypass is
      nutrient malabsorption leading to deficiencies of iron, fat-soluble vitamins and vitamin B12.
      The malabsorption of drugs, many of which are designed to be maximally absorbed in the upper
      small intestine, is also a major potential concern. Surprisingly, this issue has received
      surprisingly little attention in the published literature. A number of factors may
      contributed to reduced absorption post-bypass, delayed gastric emptying, reduced intestinal
      transit time, diminished opportunity for mucosal exposure, and changes in drug solubility
      resulting from alterations in intestinal pH.

      Azithromycin, a macrolide antibiotic that interferes with ribosomal protein synthesis, is
      indicated for the treatment of respiratory tract, skin/soft tissue, sinus and pelvic
      infections. Azithromycin is most commonly prescribed orally for the treatment of
      community-acquired pneumonia (CAP), and is recommended as first-line treatment in patients
      with this condition who are being managed on an outpatient basis. CAP accounts for over 1
      million physician visits, 60 000 hospital admissions, 640 000 days of restricted activity and
      (together with influenza) is the 6th leading cause of death in the United States. In
      Edmonton, at least 50% of CAP is managed as with outpatient therapy. Post-bariatric surgery
      patients who develop CAP and are treated with outpatient oral antibiotics would clearly be at
      risk of treatment failure if the antibiotic is not optimally absorbed. Treatment failure may
      pose a significant risk of respiratory complications or death. Unfortunately, no studies have
      examined the absorption of antibiotics post-gastric bypass. Because, azithromycin is
      intrinsically poorly absorbed, with a bioavailability of only 38%, suboptimal absorption
      post-gastric bypass is a major concern. The purpose of this study is to determine whether
      gastric bypass results in clinically significant reductions in azithromycin absorption.
    

Intervention name(s): Azithromycin
Intervention type(s): Drug
Intervention description(s): 500 mg single dose
Other intervention name(s): Zithromax
Intervention MeSH terms: Azithromycin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: drug absorption; azithromycin; obesity; bariatric surgery