Absorption of Drugs Post-Bariatric Surgery (Absorb-Azithromycin)
关键词
抽象
描述
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.
日期
最后验证: | 06/30/2011 |
首次提交: | 06/20/2010 |
提交的预估入学人数: | 06/29/2010 |
首次发布: | 06/30/2010 |
上次提交的更新: | 07/27/2011 |
最近更新发布: | 07/28/2011 |
实际学习开始日期: | 05/31/2010 |
预计主要完成日期: | 06/30/2011 |
预计完成日期: | 06/30/2011 |
状况或疾病
干预/治疗
Drug: Azithromycin
相
手臂组
臂 | 干预/治疗 |
---|---|
Active Comparator: Post Roux-en-Y gastric bypass Post-bypass receiving a single dose of azithromycin | |
Active Comparator: Controls BMI and sex matched. Have not undergone surgery |
资格标准
有资格学习的年龄 | 18 Years 至 18 Years |
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Male and Female 2. 18 - 60 years old 3. ≥ 3 months post-RYGB surgery or a suitable control for bariatric surgery 4. Able to provide written informed consent. Exclusion Criteria: 1. Undergone or undergoing reversal of a previous bariatric procedure which involves further resection or bypass of the intestine. 2. Any major post-operative gastrointestinal complications, such as an anastomotic leak, outlet obstruction or persistent vomiting 3. Currently on azithromycin therapy 4. Any contraindications to azithromycin therapy such as: - Allergy or hypersensitivity to the drug - liver failure or baseline liver enzymes higher than 3-fold above the upper limit of normal - end-stage renal failure (glomerular filtration rate < 10 ml/min) - macrolide hypersensitivity - history of torsade de pointes or baseline QTc interval ≥ 500 ms - acute illness 5. Pregnant or nursing 6. Concomitant treatment with septra, anti-HIV drugs, digoxin, disopyramide, ergotamine, dihydroergotamine, triazolam, antihistamines (terfenadine, astemizole) and theophylline is also a contraindication to enrolment because of the potential for drug interactions that would affect the blood concentrations of azithromycin or these agents. 7. Any other medical, social or geographic condition, which, in the opinion of the investigator would not allow safe completion of the study protocol. |
结果
主要结果指标
1. Azithromycin absorption [Blood samples for analysis of azithromycin levels collected at 0, 0.5, 1, 1.5, 2, 3, 5, 7 and 24 hours post-dose.]
次要成果指标
1. Tmax [instant]
2. Cmax [instant]