The use of pantoprazole and famotidine in gastroesophageal reflux disease

Gastroesophageal reflux disease is one of the most common diseases of the gastrointestinal tract, the incidence is comparable in men and women and increases with age (especially after the age of 40). The essence of the disease is the reflux of acid gastric contents into the lumen of the esophagus and causing local irritation of the mucosa. The main symptom of gastroesophageal reflux disease is heartburn, i.e. a burning sensation behind the breastbone, often aggravated after a heavy and fatty meal or a change in body position (by bending down, lying down). Symptoms, including extra-esophageal symptoms, can also occur at night (even in 45–80% of gastroesophageal reflux disease patients) and are not always immediately associated with reflux. The mainstay of treatment are acid-inhibiting drugs. The purpose of this article is to discuss, on a case-by-case basis, the beneficial combination of pantoprazole with famotidine for symptom control and quality of life improvement.

Laparosacopic management with combination of fatty meal and methylen-blu for chylous leak after a left para-aortic paraganglioma excision

We report a case of chylous leak recognized post-operatively after abdominal surgery for left para-aortic paraganglioma in a young female with a history of open botallo’s duct. Conservative measures failed to control the leak and the patient is not eligible for sclerotisation. Laparoscopic exploration with intralipidand methylen blue injection through an orogastric tube revealed the leaking area near the superior mesenteric vein behind the Traitz, and this was ligated with non-asorbable suture and placement of acrylic glue. The patient was discharged the 7th post-operative day after removal of the drainage which appeared to supply <100 cc of serum material. Outpatient control was successful and the patient is actually in good conditions.

In Silico Food-Drug Interaction: A Case Study of Eluxadoline and Fatty Meal

Food-drug interaction is an infrequently considered aspect in clinical practice. Usually, drugs are taken together with meals and what follows may adversely affect pharmacokinetic and pharmacodynamic properties, and hence, the therapeutic effects. In this study, a computational protocol was proposed to explain the different assimilations of two µ-receptors agonists, eluxadoline and loperamide, with a peculiar pharmacokinetic profile. Compared to loperamide, eluxadoline is absorbed less after the intake of a fatty meal, and the LogP values do not explain this event. Firstly, keeping in mind the different pH in the intestinal tract, the protonation states of both compounds were calculated. Then, all structures were subjected to a conformational search by using MonteCarlo and Molecular Dynamics methods, with solvation terms mimicking the water and weak polar solvent (octanol). Both computational results showed that eluxadoline has less conformational freedom in octanol, unlike loperamide, which exhibits constant behavior in both solvents. Therefore, we hypothesize that fatty meal causes the “closure” of the eluxadoline molecule to prevent the exposure of the polar groups and their interaction with water, necessary for the drug absorption. Based on our results, this work could be a reasonable “case study”, useful for future investigation of the drug pharmacokinetic profile.

Evaluation of Gall Bladder Volume in Type 2 Diabetes Mellitus Patients Using Real Time Ultrasonography

Background: Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Autonomic neuropathy manifests as esophageal dysfunction, nocturnal diarrhea, gall bladder dysfunction, sphincter disturbances, atonic bladder and orthostatic hypotension. The present study aimed to evaluate and compare the gall bladder volume in fasting and post prandial state by real time ultrasound in Type 2 Diabetes Mellitus (T2DM) patients and healthy controls. Subjects and Methods: In this cross sectional study, 90 subjects were included. Among them, 45 were type 2 diabetes mellitus patients included as cases and 45 age and sex matched healthy controls, who attended the Department of Medicine and Radio-diagnosis, Akash Institute of Medical Sciences & Research Centre, Devanahalli, Bengaluru, Karnaaka. All the study subjects were underwent detailed general and systemic examinations. Under aseptic conditions, 3ml fasting blood samples were collected and used for the estimation of fasting blood sugar, post prandial blood sugar. Gall bladder volume evaluation in fasting and 45 minutes post prandial (standardized fatty meal) state were done in T2DM patients and controls using real time ultrasound (GE Voluson P8 Mechine). Results: In the present study, BMI (24.78 2.31 kg/m2), FBS (160.98 27.99 mg/dl), PPBS (244.31 38.91 mg/dl), Fasting gall bladder volume (33.33 6.42 cm3), post fatty meal gall bladder volume (15.21 6.39 cm3), ejection fraction (49.34 17.29 cm3) were significantly increased in type 2 diabetes mellitus patients compared with healthy controls. Conclusion: The study results conclude that, fasting and post-prandial gallbladder volumes are indicative of gallbladder function. Patients with type 2 diabetes mellitus showed statistically significant impairment of gallbladder function. Gallbladder function may be evaluated routinely in type 2 diabetes mellitus patients.

Effect of Dietary Macronutrients on Postprandial Glucagon and Insulin Release in Obese and Normal-Weight Women

The aim of the study was to assess the effect of dietary macronutrients on circulating glucagon and insulin levels in obese and normal-weight women. Potentially, the impaired release of glucagon may proceed abnormal glucose metabolism in obese patients ahead of overt diabetes. In 20 insulin-sensitive women (11 obese and 9 normal-weight), plasma concentrations of insulin and glucagon levels were assessed before and after 3 different macronutrient test meals. AUCtotal insulin in the obese group was increased after protein and carbohydrates compared to fatty test meal consumption (3981 ± 2171 and 4869 ± 2784 vs. 2349 ± 1004 μIU∗h/m, p<0.05, respectively), but without a difference between protein and carbohydrates ingestion. However, in the normal-weight group, AUCtotal insulin was increased after carbohydrates compared to fatty test meal ingestion (3929 ± 1719 vs. 2231 ± 509 μIU∗h/ml, p<0.05) and similar after carbohydrate and protein as well as after fatty and protein test meals (3929 ± 1719 vs. 2231 ± 509 vs. 3046 ± 1406 μIU∗h/ml, respectively). However, AUCtotal insulin was significantly increased in obese compared to normal-weight women only after carbohydrate test meal ingestion (4869 ± 2784 vs. 3929 ± 1719 μIU∗h/ml, p<0.05). AUCtotal glucagon was similar after carbohydrate, protein, and fatty test meals ingestion in obese and normal-weight women (921 ± 356 vs. 957 ± 368 vs. 926 ± 262 ng∗h/ml and 1196 ± 14 vs. 1360 ± 662 vs. 1792 ± 1176 ng∗h/ml, respectively). AUCtotal glucagon was significantly lower in obese than normal-weight women after a fatty meal (926 ± 262 vs. 1792 ± 1176 ng∗h/ml, p<0.01). Postprandial glucagon secretion is not related to the macronutrient composition of the meal in normal-weight women since postprandial glucagon concentrations were stable and did not change after carbohydrate, protein, and fatty test meals. Lower glucagon secretion was observed in obese subjects after fatty meal consumption when compared to normal-weight subjects. Postprandial insulin profile was significantly higher after carbohydrate than fatty test meal intake in the obese group and did not differ between obese and normal-weight groups after carbohydrate, protein, and fatty test meals consumption. Impaired glucagon secretion after fatty meat suggests early pancreatic alpha-cell dysfunction, after a carbohydrate meal is a compensatory mechanism.

SAT-LB6 First Human Trial of an Oral Native Testosterone Shows Physiological Levels of Testosterone and Dht in Both Fasted and Fed State in Hypogonadal Men

Introduction: The prevalence of male hypogonadism is estimated to be 6% in the USA (1). Current therapies have limited acceptability: gels can be messy and risk inadvertent dosing of others; injections are painful; and oral testosterone undecanoate (TU) delivers variable testosterone levels, requires concurrent ingestion of a fatty meal and may produce supraphysiological dihydrotestosterone (DHT) levels. We present the first human trial of an oral native testosterone preparation formulated to deliver physiological levels of testosterone irrespective of food intake. Aim: To compare the pharmacokinetics of DITEST (Diurnal Ltd Cardiff, UK) to an oil based oral TU formulation (Andriol Testocaps MSD, UK) and explore the effect of food on DITEST bioavailability. Methods: Single centre, phase 1b study of DITEST in 25 adult males with hypogonadism, one subject withdrawn after single period and only included in safety analysis (Clinicaltrials.gov: NCT02966652). Part 1 compared the pharmacokinetics of 80mg TU with 120mg DITEST after a high fat meal. Part 2 the pharmacokinetics of 200mg of DITEST administered in either fed or fasted states. Results are baseline adjusted. Results: DITEST showed a testosterone dose response between 120mg and 200mg with Cmax 550 (19.1) and 877 (30.4) ng/dl (nmol/l) and AUC0-10h 59.5 and 88.6 h*nmol/L. DITEST 200mg gave an equivalent Cmax and AUC0-10h to TU 80mg: Cmax 877 (30.4) vs 906 (31.4) ng/dl (nmol/l) and AUC0-10h 88.6 vs 102 h*nmol/L. Fed and fasted DITEST had similar pharmacokinetics: Cmax 764 (26.5) vs 877 (30.4) ng/dl (nmol/L), AUC0-10h 87.0 vs 88.6. DITEST resulted in lower levels of DHT than TU: Cmax 84 (2.9), 131 (4.5) & 194 (6.7) ng/dl (nmol/l); AUC0-10h 11.0, 16.7 & 36.3 h*nmol/L for DITEST 120mg, 200mg & 80mg TU, respectively. There was one serious adverse event (urinary retention) in the study during TU dosing. There were no emerging safety concerns, and adverse event frequency and severity was similar between the two treatments. Discussion: These results demonstrate that 200mg DITEST provides similar testosterone exposure with more physiological DHT exposure than 80mg TU given with a high fat meal. Administration of DITEST in fed and fasted states provides similar testosterone and DHT exposure. Compared to published literature on a self-emulsifying formulation of TU at 200mg, DITEST at 200mg provides a similar testosterone Cmax and no requirement for a fatty meal (2). Conclusion: DITEST is an oral native testosterone formulation with anticipated advantages over current oral therapy of dosing without food and a lower risk of supraphysiological DHT levels. References: 1. Basaria S. Male hypogonadism. Lancet 2014; 383:1250-1263. 2. Yin AY, et al., J Androl 2012; 33:190-201.

Comparison of Fatty Meal, Drotaverine and Hyoscine for Duodenal Anti-motility and Cannulation During ERCP- A Randomised Controlled Trial

Introduction: Endoscopic Retrograde Cholangiopancreatography (ERCP) is a technically demanding procedure that requires considerable amount of training to be performed safely. Successful cannulation of the ducts depends on the expertise of the endoscopist. Conventionally, cannulation is facilitated with the help of smooth muscle relaxants like Hyoscine-N-butyl bromide or Drotaverine which impair duodenal contractions and facilitate sphincter of oddi relaxation. Aim: To compare the effect of Fatty meal versus Drotaverine hydrochloride versus Hyoscine-N-butyl bromide on duodenal contraction rate, ease of identification of the papillary orifice, time for cannulation, and adverse effects of agents used on haemodynamic parameters. Materials and Methods: The study was conducted at Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai,Tamil Nadu, India, where 60 patients admitted for ERCP with normal appearing ampulla, were taken-up for the study. Patients were subjected randomly into the three groups viz., Hyoscine group, Drotaverine group and Fatty meal group. In Fatty meal group, 200 mL of semi skimmed milk (1.7% fat) was given orally one hour prior to the procedure to allow for gastric emptying. A 20 mg of intravenous Hyoscine-N-butyl bromide and 40 mg of intravenous Drotaverine hydrochloride were administered 15 minutes before procedure in Hyoscine and Drotaverine group, respectively. Statistical analysis was done by Chi-square test and Analysis of Variance (ANOVA) test and using Statistical Package for the Social Sciences (SPSS) 16.0 version software. A p-value <0.05 was considered significant. Results: The difference in duodenal motility, cannulation time and success of the procedure did not show a statistically significant p-value between the three groups. The identification of ampulla was easy with the fatty meal group. The statistical analysis for intraprocedural change in pulse rate and Blood Pressure (BP) variation showed a significant p-value for Hyoscine group compared to the other two groups. The change in pulse rate for Hyoscine vs. Drotaverine vs. Fatty meal group during the procedure was 51.5±12.8 vs. 24.2±8.4 vs. 24.4±8.8 per minute, respectively. The variation in BP during the procedure was 18.3/15.7±7.7/9.0 mmHg vs. 9.0/8.7±5.7/5.6 mmHg vs. 10.4/8.6±4.6/3.3 mmHg for Hyoscine vs. Drotaverine vs. Fatty meal group respectively. Conclusion: Fatty meal is not inferior to the conventionally used Hyoscine-N-butyl bromide or Drotaverine for its anti-motility effect on the duodenum during ERCP. The cannulation time is no different within the groups. Fatty meal, the action of which is physiological may be used as a suitable alternative to antispasmodic pharmacological agents which have potential adverse effects.