Effect of Roux-en-Y gastric bypass on the bioavailability of metoprolol from immediate and controlled release tablets: a single oral dose study before and after surgery.

Objective: Roux-en-Y gastric bypass (RYGB) surgery induces major changes in the gastrointestinal tract that may alter the pharmacokinetics of orally administered drugs. Results from pharmacokinetic studies are sparse. This study aimed to investigate the effect of RYGB on the bioavailability of metoprolol from immediate release (IR) and controlled release (CR) tablets in female patient volunteers before and after surgery. Methods: An explorative, two-phase, single oral dose pharmacokinetic study of metoprolol in female patients undergoing RYGB was carried out. The dose was administered twice in each patient, 1 month before and 6 months after surgery. After intake of either 100 mg of metoprolol IR or CR tablet serum concentration-time profiles of metoprolol were determined. The endpoint was the ratio of AUCafter/AUCbefore of metoprolol. Results: Twelve patients were included in the study (metoprolol IR: 7; metoprolol CR: 5). After intake of a metoprolol IR tablet major intraindividual and interindividual differences for area under the serum concentration versus time curve (AUC) of metoprolol before and after surgery were observed (range ratio AUC0-10 hours after/AUC0-10 hours before: 0.74-1.98). For metoprolol CR tablets a significant reduction in bioavailability of metoprolol was observed after surgery (range ratio AUC0-24 hours after/AUC0-24 hours before: 0.43-0.77). Conclusion: RYGB may influence the bioavailability of metoprolol from an IR tablet. The magnitude of changes in bioavailability after RYGB requires close monitoring of patients using metoprolol IR tablets and dose adjustment if deemed necessary. RYGB clearly reduces the bioavailability of metoprolol from a CR tablet. After RYGB clinicians may consider to increase the dose according to clinical response.

Prevalence of hypoglycaemia in a random population after Roux-en-Y gastric bypass after a meal test.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinaemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB. DESIGN: This is a cross-sectional study of patients 4 years after primary RYGB. METHODS: From a total population of 550 patients, a random sample of 44 patients completed the total test procedures. A standardized mixed meal was used as stimulus. Venous blood samples were collected at baseline, every 10 min during the first half hour and every 30 min until 210 min after the start. Symptoms were assessed by questionnaires. Hypoglycaemia is defined as a blood glucose level below 3.3 mmol/L. RESULTS: The prevalence of postprandial hypoglycaemia was 48% and was asymptomatic in all patients. Development of hypoglycaemia was more frequent in patients with lower weight at surgery (P = 0.045), with higher weight loss after surgery (P = 0.011), and with higher insulin sensitivity calculated by the homeostasis model assessment indexes (HOMA2-IR, P = 0.014) and enhanced beta cell function (insulinogenic index at 20 min, P = 0.001). CONCLUSION: In a randomly selected population 4 years after primary RYGB surgery, 48% of patients developed a hypoglycaemic event during an MMTT without symptoms, suggesting the presence of hypoglycaemia unawareness in these patients. The findings in this study suggest that the pathophysiology of PHH is multifactorial.

Long-term self-reported symptom prevalence of early and late dumping in a patient population after sleeve gastrectomy, primary, and revisional gastric bypass surgery.

BACKGROUND: Early and late dumping are side effects of bariatric surgery. Almost no data are available on the prevalence of dumping after different surgical procedures. OBJECTIVES: Comparison of the relative risks of dumping in a large population of patients having undergone primary Roux-en-Y gastric bypass (pRYGB), sleeve gastrectomy (SG), or revisional RYGB (rRYGB; after removal of band). SETTING: Bariatric center of a teaching hospital. METHODS: In this descriptive cohort study, all patients who underwent a pRYGB (n = 615), SG (n = 157), or rRYGB (n = 274) between 2008 and 2011 were approached by mail and asked to complete and return a questionnaire of general and disease-specific questions related to dumping syndrome. Relative risks (RR) were calculated (mean with 95% confidence intervals) by comparing the prevalence of high suspicion for early and late dumping between different surgical procedure groups and primary gastric bypass surgery. RESULTS: The questionnaire was completed and returned by 593 (57%) of 1046 patients. Fewer patients with SG were at high suspicion of early dumping than after pRYGB (RR [95% confidence interval] .46 [.22-.99], P = .049). No differences for early dumping were seen between rRYGB and pRYGB (RR 1.21 [.77-1.91], P = .40). More patients were at high suspicion for late dumping after rRYGB compared with after pRYGB (RR 1.78 [1.09-2.90] P = .021). No differences for late dumping were seen between SG and pRYGB (RR .59 [.22-1.61], P =.30). CONCLUSION: Fewer complaints of early dumping are reported after SG, while patients report more complaints of late dumping after rRYGB compared with pRYGB.

Influence of bariatric surgery on the use of medication.

PURPOSE: Bariatric surgery can influence the prevalence and incidence of comorbidities, as well as the pharmacokinetics of drugs. This might lead to changes in the use of drugs. This study aimed to assess the influence of bariatric surgery on the use of medication in patients before and after surgery, focusing on type, number of medications, and daily dosage. METHODS: In a retrospective and prospective observational study, drug dispensing data from pharmacies of patients undergoing their first bariatric surgery between January 2008 and September 2011 was collected. Dispensing data from 1 month before until 12 months after surgery was analyzed. Drugs were classified according to the WHO-ATC classification system. Dosages of drugs were compared using defined daily dose (DDD). RESULTS: Among 450 patients, 12 months after surgery, the mean number of drugs per patient for antidiabetics, drugs acting on the cardiovascular system, anti-inflammatory and antirheumatic drugs, and drugs for obstructed airway diseases decreased by, respectively, 71.3 % (95 % CI 57.2 to 85.4), 34.5 % (95 % CI 28.2 to 43.0), 45.5 % (95 % CI 13.3 to 72.6), and 33.1 % (95 % CI 15.3 to 53.2). Patients used lower median DDD of oral antidiabetics, beta-blocking agents, and lipid-modifying drugs. CONCLUSIONS: For some major drug classes 12 months after bariatric surgery, the use of drugs decreases in terms of mean number per patient. A reduction in dose intensity was observed for oral antidiabetics, beta-blocking agents, and lipid-modifying drugs. Dispensing data from pharmacies may provide detailed information on the use of medications by patients after bariatric surgery.

Influence of bariatric surgery on the use and pharmacokinetics of some major drug classes.

The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes. Very few studies have been published on the influence of bariatric surgery on the pharmacokinetics of drugs. After bariatric surgery, theoretically, reduced drug absorption may occur. Correct dosing and choosing the right dosage form for drugs used by patients after bariatric surgery are necessary for optimal pharmacotherapy. Therefore, more clinical studies are needed on the influence of bariatric surgery on the pharmacokinetics of major drugs.

Cerebral gas embolism due to upper gastrointestinal endoscopy.

Cerebral gas embolism as a result of upper gastrointestinal endoscopy is a rare complication and bares a high morbidity. A patient is presented who underwent an upper endoscopy for evaluation of a gastric-mediastinal fistula after subtotal oesophagectomy and gastric tube reconstruction because of oesophageal cancer. During the procedure, cerebral gas emboli developed resulting in an acute left-sided hemiparesis. After hyperbaric oxygen therapy, the patient recovered almost completely. The aetiology and treatment is discussed based on the reviewed literature. Once cerebral gas emboli are recognized, patient outcome can be improved by hyperbaric oxygen therapy.

Contraceptive treatment after biliopancreatic diversion needs consensus.

BACKGROUND: An important population of patients who undergo biliopancreatic diversion (BPD) are fertile women. A consensus is needed with regard to contraceptive therapy after BPD by evaluating the risks of pregnancy, the safety of oral contraception and the changes in fertility after this bariatric surgery. METHOD: From May 1997 until May 1998, 40 women who underwent a BPD were included in a prospective study evaluating the hormone status preoperatively and postoperatively after 2 and 7 days, 3 and 6 months and 1 year. An extensive questionnaire, with regard to fertility and obstetric history, was sent at least 2 years after inclusion. A literature search was performed to understand the complex physiology of hormone changes after excess weight loss, as well as absorption and metabolism of oral contraceptives. RESULTS: Our laboratory results are consistent with hormone changes found in the literature, which show that rising levels of serum sex-hormone-binding globulin, follicle stimulating hormone and luteinizing hormone and decreasing levels of testosterone and dehydroepiandrosterone sulphate result in an improved fertility status, regulated through complex interactions, in particular with the gonatotropin-releasing-hormone pulse generator. The questionnaire shows the use of different types of contraception. From the 9 patients who only used oral contraception, 2 patients developed an unforeseen pregnancy after BPD. Although miscarriages and neonatal complications were seen in other patients in our hospital, none of these problems were seen in our study. CONCLUSION: Pregnancy should be avoided for 12 to 18 months after BPD. Fertility increases after BPD. As oral contraception is most popular and less reliable, we strongly believe that large multi-centre, prospective, randomized studies are necessary to come to a consensus about the use of contraceptive therapy after BPD.