Absorption of Drugs Post-Bariatric Surgery (Absorb-Azithromycin)

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.