Pattern Of Gastric Emptying Research Articles

Forecasting the effect of water gastric emptying patterns on model drug release in an in vitro glass-bead flow-through system.

Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an in vitro glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.

The acute effect of a β-glucan-enriched oat bread on gastric emptying, GLP-1 response, and postprandial glycaemia and insulinemia: a randomised crossover trial in healthy adults

BackgroundThe cereal fibre β-glucan reduces postprandial glycaemia, however, the underlying mechanisms are not fully understood. Thus, the aim of this study was to investigate the acute effect of a β-glucan-enriched oat bread on gastric emptying half-time (T1/2), gastric emptying lag phase (Tlag), and gastric emptying rate (GER), and the secretion of glucagon-like peptide-1 (GLP-1) as potential means to influence postprandial glycaemia.MethodsA randomised crossover trial was conducted in 22 healthy adults (age 24.6 ± 3.1 years, BMI 23.1 ± 2.7 kg/m2) receiving 25 g available carbohydrates from a β-glucan-enriched oat bread or a control whole-wheat bread at two non-consecutive days. T1/2, Tlag, and GER were determined based on ultrasound measures of the cross-sectional gastric antrum area in the fasting state and 15, 30, 45, 60, 90, and 120 min postprandially. Capillary glucose, serum insulin, and plasma GLP-1 concentrations were measured at the same time points.ResultsA biphasic pattern of gastric emptying with a distinct Tlag before the commencement of emptying was observed in most subjects for both bread types. While no differences in GER were evident (p = 0.562), consumption of the oat bread significantly increased T1/2 by 18 min and Tlag by 14 min compared with the whole-wheat bread (p = 0.005 and p = 0.010, respectively). In addition, the oat bread significantly reduced iAUC2h for glucose and insulin responses compared with the whole-wheat bread (p = 0.001 and p < 0.001, respectively). There were no significant differences in GLP-1 response between the two breads (p = 0.892).ConclusionThe increased T1/2 and Tlag could offer a potential mechanism for the observed attenuation of postprandial glycaemia and insulinemia after consumption of the β-glucan-enriched oat bread compared with the whole-wheat bread.Trial registration: The study is registered at clinicaltrails.gov (NCT04571866).

Universal Fasting Glucose Screening Before Gastric Emptying Scintigraphy and the High Prevalence of Undiagnosed Diabetes and Prediabetes.

The aim of this study was to assess the rates of undiagnosed diabetes mellitus (DM) and pre-DM in patients undergoing gastric emptying scintigraphy (GES). Diabetes is an epidemic in the United States, and the disease is associated with altered gut motility. As a result, we suspected that a significant number of patients referred for GES may have undiagnosed DM or pre-DM. Given that established procedure standards for GES require all patients to prepare with an 8-h fast, an opportunity is provided to measure the fasting blood glucose (FBG) in all individuals before they undergo the examination. Methods: The charts of patients undergoing GES were reviewed for a history of DM and correlated with FBG and GES results. FBG values, obtained by point-of-care testing, were categorized as normal, pre-DM, or DM. Results: Patients with known DM made up 23% of those referred for GES, and most (55%) had a normal FBG. In those without a history of DM, there were a significant number with undiagnosed pre-DM (12%) and DM (33%). Conclusion: Our study provides the first measure of the likely prevalence of undiagnosed DM and pre-DM and characterizes the different gastric emptying patterns among patients with normal FBG, likely undiagnosed pre-DM, likely undiagnosed DM, and known DM.

Impact of food viscosity on in vitro gastric emptying using dynamic and semi-dynamic models

Viscosity has been shown to affect food breakdown and nutrient release in the gastrointestinal tract, and the subsequent postprandial glycaemic response and satiety. However, the correlation between food viscosity and gastric emptying is not fully understood. This study investigated the in vitro gastric emptying behavior of peanut butter with different viscosities using semi-dynamic and the artificial gastric digestive system (AGDS) models. Results from both digestion models showed that high viscosity peanut butter had a slower pH decrease, higher buffering capacity, slower phase separation of gastric chyme and less protein hydrolysis and lipid digestion than the control and low viscosity groups. However, the AGDS displayed slower gastric emptying rate, smaller chyme particle size and less proteolysis than the semi-dynamic model, particularly in the high-viscosity group (e.g. ∼60% of gastric emptying rate for AGDS and ∼20% for semi-dynamic model at 120 min), due to the different mechanical shearing forces and gastric emptying patterns in these two models. This study demonstrated the role of food viscosity on the gastric emptying process, and it also suggested that viscosity should be taken into account when designing future functional foods with particular structure.

Modeling digestion, absorption, and ketogenesis after administration of tricaprilin formulations to humans

At present, tricaprilin is used as a ketogenic source for the management of mild to moderate Alzheimer’s disease. After administration of the medium-chain triglyceride, tricaprilin is hydrolyzed to octanoic acid and further metabolized to ketones, acting as an alternative energy substrate for the brain. In this investigation, we developed a physiologically-based biopharmaceutics model simulating in vivo processes following the peroral administration of tricaprilin. The model includes multiple data sources to establish a partially verified framework for the simulation of plasma profiles. The input parameters were identified based on existing literature data and in vitro digestion studies. Model validation was conducted using the data from a phase I clinical trial. A partial parameter sensitivity analysis elucidated various influences on the plasma ketone levels that are mainly responsible for the therapeutic effects of tricaprilin. Based on our findings, we concluded that dispersibility and lipolysis of tricaprilin together with the gastric emptying patterns are limiting ketogenesis, while other steps such as the conversion of octanoic acid to ketone bodies play a minor role only.

Tolerability, gastric emptying patterns, and symptoms during the Nottingham Test Meal in 330 secondary care non-diabetic dyspeptic patients.

Scintigraphy is used for overall assessment of gastric emptying. Adherence to an international consensus protocol is recommended to ensure quality; however, this has not been widely adopted because preparation of the "egg-beater" meal is inconvenient in clinical practice. In this report, we audit the tolerability and the results of gastric emptying scintigraphy with the 400 ml Tc-99 m-labeled liquid nutrient Nottingham Test Meal (NTM). Results from 330 consecutive adult, non-diabetic patients with dyspeptic symptoms referred for gastric scintigraphy were analyzed. Gastric half-emptying time (T50) and validated measurements of early- and late-phase gastric emptying were acquired. Postprandial sensations of fullness, bloating, heartburn, nausea, and epigastric pain were recorded using 100 mm visual analog scales (VAS) before and 0, 30, and 90 min after NTM ingestion. Results were compared with those previously obtained in healthy subjects. Almost all (98%) of the patients were able to consume the 400 ml NTM. Considering early- and late-phase gastric emptying, frequently observed patterns included normal early- with slow late-phase (25%) and fast early- with slow late-phase emptying (27%). Abnormal score of fullness and/ or dyspeptic symptoms were observed in 88% of dyspeptic patients. Abnormal fullness at T0 (after completed drink ingestion) was associated with slow late phase of gastric emptying, especially in women. Gastric scintigraphy with the NTM is simple to perform and well tolerated. Whether the identified abnormal gastric emptying patterns could predict different treatment outcome in patients with functional dyspepsia is the subject of ongoing prospective studies.

Comparison of Gastric Emptying Time after the Ingestion of Whisky with Isocalorically Adjusted Glucose Solution.

Previous studies have shown that the liquid gastric emptying mainly depended on energy content, regardless of compositional differences. But the gastric emptying of alcoholic beverages remains unclear. Therefore, we performed the present study to compare gastric emptying times between whisky mixed with water and glucose solution with uniform energy contents and volumes. As a crossover study, 10 healthy male volunteers ingested one of 3 test solutions with a uniform volume of 150 ml, i.e., whisky with water-containing whisky 30 ml (67 kcal), sugar water containing glucose 16.8 g (67 kcal), and water (0 kcal), and the gastric emptying time of each beverage was then assessed by ultrasound measurements of the gastric antral cross-sectional area. The gastric emptying pattern of whisky with water was faster than that of isocaloric sugar water, but slower than that of water. Each antral cross-sectional area 20, 30, and 40 min after the ingestion of sugar water was significantly larger than that of whisky with water. Antral cross-sectional areas 10 and 20 min after the ingestion of water were significantly smaller than those of whisky with water. In conclusion, the gastric emptying time of whisky would be faster than that of isocaloric glucose solution and slower than that of water. Unlike the other beverages, the gastric emptying time of alcohol drinks does not purely depend on the energy content because alcohol itself has no calorie before absorption. This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000034443).

Diabetic visceral neuropathy of gastroparesis: Gastric mucosal innervation and clinical significance.

The pathogenesis of diabetic gastroparesis due to visceral neuropathy involves multidimensional mechanisms with limited exploration of gastric mucosal innervation. This study aimed to examine quantitatively this topic and its relationship with gastroparesis symptoms and gastric emptying in diabetes. We prospectively enrolled 22 patients with type 2 diabetes and gastroparesis symptoms and 25 age- and gender-matched healthy controls for comparison. The assessments included: (i) neuropathology with quantification of gastric mucosal innervation density (MID) on endoscopic biopsy; (ii) clinical manifestations based on the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire; and (iii) functional tests of gastric emptying scintigraphy (GES). In patients with diabetes, stomach fullness, bloating and feeling excessively full after meals constituted the most common GCSI symptoms. Seven patients with diabetes (32%) had prolonged gastric emptying patterns. In diabetes, gastric MID was significantly lower in all the regions examined compared with the controls: antrum (294.8±237.0 vs. 644.0±222.0mm/mm3 ; p<0.001), body (292.2±239.0 vs. 652.6±260.9mm/mm3 ; p<0.001), and fundus (238.0±109.1 vs. 657.2±332.8mm/mm3 ; p<0.001). Gastric MID was negatively correlated with gastroparesis symptoms and total scores on the GCSI (p<0.001). Furthermore, gastric MID in the fundus was negatively correlated with fasting glucose and glycated hemoglobin levels. Gastric emptying variables, including half emptying time and gastric retention, were prolonged in patients with diabetes, and gastric retention at 3h was correlated with fasting glucose level. In diabetes, gastric MID was reduced and GES parameters were prolonged. Both were correlated with gastroparesis symptoms and glycemic control. These findings provide pathology and functional biomarkers for diabetic visceral neuropathy of gastroparesis and underlying pathophysiology.

Gastric emptying pattern and disintegration kinetics of cooked rice in a 3D printed in vitro dynamic digestion model ARK®

Abstract Understanding the gastric digestion process is essential for evaluating the bioaccessibility of nutrients from food matrices. The objective of this study was to investigate the kinetics of disintegration and gastric emptying patterns in a 3D printed stomach (ARK®) with white rice as the study sample. Modified power exponential model was used to fit the gastric retention data and the average t 1/2 and t lag values of the solid fractions were found to be 109.22 ± 4.20 and 84.16 ± 5.72 min, respectively. During the disintegration process, the weight percentage of medium size particles (∼0.35 mm) was found to be higher at 30 and 60 min. Moreover, there was a sharp decrease in the percentage of fine particles (&lt;0.125 mm) at 90 and 120 min. The ARK® could effectively mimic the physiochemical process of the human stomach, providing promising insights for future studies on the development of novel and functional food products.

Short Communication: The effects of physical feed properties on gastric emptying in pigs measured with the 13C breath test

The performance of pigs is affected by the rate of nutrient absorption in the gastrointestinal tract, which depends in turn strongly on the rate of stomach emptying. The 13C breath test provides a non-invasive diagnostic tool to measure gastric emptying patterns. Despite the wide acceptance of this method in human intervention studies, it has not found its way to the domain of animal sciences. In this study, we used the breath test to measure gastric emptying in young growing pigs using [1-13C] octanoic acid to trace digesta solids and [1-13C] glycine to study liquids. Pigs were fed a starch-rich diet, varying in starch source (isolated starch from barley, maize or high-amylose maize) or form (isolated barley starch, ground barley or extruded barley), after which 13CO2 enrichment was frequently measured during 11 h. Outliers in 13CO2 enrichment in the response curve of each pig were identified with a Cookʼs distance outlier test in combination with a leave-one-out analysis. Effects of experimental treatments on breath test parameters were tested using a GLM. In general, pigs were easy to train and the tailor-made mask allowed effortless sampling. Gastric emptying of all pigs followed a biphasic pattern, with a higher 13C recovery during the first peak. The first peak in gastric emptying of solids reached its maximum enrichment within 2 h after feeding in all cases. For digesta liquids, this peak was reached earlier for pigs fed ground barley (2.2 h after feeding), compared to pigs fed diets containing isolated starch (2.8 h after feeding). The second peak in gastric emptying of solids was reached later for pigs fed ground barley (5.9 h after feeding), compared with pigs fed extruded barley (4.5 h after feeding) and pigs fed diets containing isolated barley starch (4.8 h after feeding). In conclusion, the 13C breath test is a convenient, non-invasive tool to gain more insights into the gastric emptying pattern of pigs.

1248 Late Onset Rapid Gastric Emptying: A New Entity to Explain Post-Prandial Symptoms

INTRODUCTION: Symptomatic patients with a suspected upper GI dysmotility disorder may have a normal 4 hour gastric emptying (GE) using the standardized radioisotope labeled egg beater meal methodology and do not meet criteria for the diagnosis of either delayed or rapid gastric emptying. We propose conservative thresholds to identify abnormal gastric emptying patterns among such symptomatic patients determined to have normal gastric emptying (NGE) in order to classify a subset as meeting criteria for a new entity, late-onset rapid gastric emptying (LRGE). METHODS: We recruited and conducted IRB approved standardized 4-h GE studies on 19 healthy normal subjects (Mean age 49, 68% females, 68% Hispanics) and in 425 patients (Mean age 51, 80% females, 69% Hispanics, and 33% with diabetes) who had symptoms suggesting an upper GI dysmotility disorder and referred for a standardized 4-h GES from 2009 to 2015. Patients had postprandial symptoms ranging from nausea, early satiety, fullness, epigastric pain, stool urgency, and bloating. Their GES was reported as normal based on no rapid gastric emptying at 1 h or delayed GE at 2 or 4 hrs. The 95% upper reference limits for the decrement percentages in gastric retention values from 1-2 h, 2-3 h and 3-4 h were determined using normal distribution in the 19 healthy normal subjects. These thresholds were applied to from the 425 NGE patients referred from 2009-2015. A 95% confidence interval (CI) of LRGE prevalence was determined. RESULTS: Approximately 5% of patients who had normal standardized 4-h GES results had an abnormal GE pattern based on the proposed criteria for late-onset rapid gastric emptying. Our data raises awareness to apply the gastric emptying decrement cut offs we have established to identify the diagnosis of LRGE in patients who otherwise would be interpreted as having normal GE and this will enable an explanation and management for their postprandial symptom profile. CONCLUSION: Approximately 5% of patients who had normal standardized 4-h GES results had an abnormal GE pattern based on the proposed criteria for late-onset rapid gastric emptying. Our data raises awareness to apply the gastric emptying decrement cut offs we have established to identify the diagnosis of LRGE in patients who otherwise would be interpreted as having normal GE and this will enable an explanation and management for their postprandial symptom profile.

A Simulated Stomach Duodenum Model Predicting the Effect of Fluid Volume and Prandial Gastric Flow Patterns on Nifedipine Pharmacokinetics From Cosolvent-Based Capsules

Nifedipine is a Biopharmaceutics Classification System class II drug displaying large variability in absorption even when administered as immediate-release soft gelatin capsules of a cosolvent formulation. This in vitro study sought to understand the reasons behind variability in nifedipine absorption, how it can be minimized, and if it can be predicted using in vitro models. A dynamic in vitro simulated stomach duodenum model was used to explore drug concentration–time profiles of nifedipine soft gelatin capsules under conditions simulating how patients take their medicines. Specifically, the effect of prandial gastric emptying patterns and fluid volume administration (250 mL vs. 50 mL water) were investigated. Significant supersaturation of nifedipine was observed. While administration of large and small water volumes gave rise to a similar Cmax and area under the curve (AUC∞), the coefficient of variation in AUC was 4.8% and 49%, respectively, which can be attributed to differences in precipitation kinetics. Fasting and fed gastric emptying patterns also gave rise to a similar AUC; however, Cmax was significantly lower in the fed state. These trends are consistent with previously published in vivo results in healthy volunteers. The simulated stomach duodenum provides a good discriminative screening tool for predicting trends in drug concentration profiles of Biopharmaceutics Classification System class II drugs.

Effects of a Gluten-Containing Meal on Gastric Emptying and Gallbladder Contraction

The ingestion of gluten has been associated with gastrointestinal symptoms even in the absence of detectable immune responses. Little is known about the pathophysiological effects of gluten on the upper gastrointestinal tract. We aimed to assess whether the ingestion of gluten leads to an impairment of the physiological mechanisms of gastric emptying, gallbladder contraction and relaxation. A total of 17 healthy subjects underwent ultrasound evaluation of gastric emptying dynamics and gallbladder contractions at baseline and every 30 min after a standard gluten-containing and gluten-free meal (250 kcal, 70% carbohydrates). The pattern of gastric emptying was similar after a standard meal with or without gluten, but differed in terms of the peak of the antral filling curve, which was wider (mean area 5.69, median 4.70, range 3.71‒9.27 cm2 vs. mean 4.89, median 4.57, 2.27‒10.22 cm2, p = 0.023) after the gluten-containing meal. The pattern of gallbladder contractions was different after the gluten-free meal (p < 0.05), with higher gallbladder volumes in the late refilling phases. The results of this study show that gluten ingestion exerts objective effects on gastric and gallbladder motility. Although the underlying pathophysiological mechanism remains unknown, these results could account for some of the gluten-related symptoms reported by patients with celiac disease and non-celiac gluten sensitivity.

Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects

The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical “gold standard”, gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system’s usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively.

Clinical features of gastric emptying after distal gastrectomy.

PurposeGastric emptying may influence the quality of life of patients who undergo distal gastrectomy. Little is known, however, about gastric emptying after distal gastrectomy. The aim of our study was to investigate gastric emptying patterns after distal gastrectomy.MethodsThis gastric-emptying study investigated patients who underwent distal gastrectomy in the 6 months or more before May 2008 to July 2013 at Chungbuk National University Hospital with a study sample of 205 patients. We analyzed patterns of gastric emptying.ResultsDelayed gastric emptying was found in 109 of the 205 patients (53.2%). Food stasis was more frequent in a group with delayed gastric emptying. In multivariate analysis, risk factors for gastroparesis were laparoscopic operation (hazard ratio [HR], 2.731; P = 0.008) and duration of less than 24 months after distal gastrectomy (HR, 2.795; P = 0.001). Delayed gastric emptying tended to decrease with duration of the postoperative period.ConclusionDelayed gastric emptying is common in distal gastrectomy, and is related to laparoscopic operation and duration of the postoperative period. Food stasis was more frequent in a group with delayed gastric emptying.

Delayed gastric emptying does not normalize after gluten withdrawal in adult celiac disease

ABSTRACTObjective Delayed gastric emptying has been frequently detected in patients with untreated celiac disease. According to several studies, gluten withdrawal showed to be effective in normalizing the gastric emptying rate. The aim of this study was to evaluate the gastric emptying rate of solids in patients with celiac disease before and after a gluten-free diet. Methods Twelve adult patients with celiac disease (age range 20–57 years) and 30 healthy controls (age range 30–54 years) underwent a 13C-octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (tlag) were calculated. After at least 12 months of a gluten-free diet, celiac patients underwent a new 13C-octanoic acid breath test. A symptom score was utilized to detect dyspeptic and malabsorption symptoms in all the patients. Results The gastric motility parameters, t1/2 and tlag, were significantly longer in patients than in controls. On a gluten-free diet, surprisingly, the gastric emptying did not normalize despite an improvement of symptom score. No significant correlation between abnormal gastric emptying and specific symptom patterns, anthropometric parameters or severity of histological damage was found. Conclusions This finding supports the hypothesis that gluten-driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing gut hormone function. The persistence of these abnormalities on a gluten free diet suggests the presence of a persistent low-grade mucosal inflammation with a permanent perturbation of the neuro-immunomodulatory regulation.

Spectrum of Gastric Emptying Patterns in Adult Patients Following Lung Transplantation

Spectrum of Gastric Emptying Patterns in Adult Patients Following Lung Transplantation

Association Between Postprandial Symptoms and Gastric Emptying After Sleeve Gastrectomy

Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric procedure. However, postprandial symptoms can compromise its beneficial effect. It is not known if a changed gastric emptying and these symptoms are related. This study aimed to assess the association between postprandial symptoms and the gastric emptying pattern after LSG. A gastric emptying study with a solid and liquid meal component was performed in the second year after LSG. Before the test, symptoms were assessed using a standardized questionnaire, and during the test, symptoms were scored on a visual analog scale (VAS). Gastric emptying results were expressed as lag phase, half time of gastric emptying (T½), and caloric emptying rate/minute. Twenty patients (14 F/6 M; age 45.6 ± 7.7 years, weight 93.4 ± 28.2 kg, BMI 31.6 ± 8.1 kg/m(2)) participated in this study; 13 had a low symptom score (≤9, group I), 7 a high symptom score (≥18, group II). VAS scores for epigastric pain, nausea, and belching were significantly higher in group II. Lag phase (solid) was 6.4 ± 4.5 min in group I, 7.3 ± 6.3 in group II (p = 0.94); T½ (solid) was 40.6 ± 10.0 min in group I, 34.4 ± 9.3 in group II (p = 0.27); caloric emptying rate was 3.9 ± 0.6 kcal/min in group I, 3.9 ± 1.0 kcal/min in group II (p = 0.32). Patients with postprandial symptoms after LSG reported more symptoms during the gastric emptying study than patients without symptoms. However, there was no difference between gastric emptying characteristics between both groups, suggesting that abnormal gastric emptying is not a major determinant of postprandial symptoms after LSG.

Effect of surfactants, gastric emptying, and dosage form on supersaturation of dipyridamole in an in vitro model simulating the stomach and duodenum.

The purpose of this study was to investigate the influence of gastric emptying patterns, surfactants, and dosage form on the supersaturation of a poorly soluble weakly basic drug, dipyridamole, using an in vitro model mimicking the dynamic environment of the upper gastrointestinal tract, and, furthermore, to evaluate the usefulness of this model in establishing correlations to in vivo bioavailability for drugs with solubility/dissolution limited absorption. A simulated stomach duodenum model comprising four compartments was used to assess supersaturation and precipitation kinetics as a function of time. It integrates physiologically relevant fluid volumes, fluid transfer rates, and pH changes of the upper GI tract. Monoexponential gastric emptying patterns simulating the fasted state were compared to linear gastric emptying patterns simulating the fed state. The effect of different surfactants commonly used in oral preparations, specifically, sodium lauryl sulfate (SLS), poloxamer-188, and polysorbate-80, on dipyridamole supersaturation was investigated while maintaining surface tension of the simulated gastric fluids at physiological levels and without obtaining artificial micellar solubilization of the drug. The supersaturation behavior of different dose strengths of dipyridamole was explored. Significant levels of dipyridamole supersaturation were observed in the duodenal compartment under all the different in vivo relevant conditions explored. Dipyridamole supersaturation ratios of up to 11-fold have been observed, and supersaturation has been maintained for up to 120 min. Lower duodenal concentrations of dipyridamole were observed under linear gastric emptying patterns compared to mononexponential gastric emptying. The mean duodenal area under concentration-time curves (AUC60min) for the dipyridamole concentration profile in the duodenal compartment is significantly different for all the surfactants explored (P < 0.05). Our investigations with the different surfactants and comparison of dosage form (solution versus suspension) on the precipitation of dipyridamole revealed that crystal growth, rather than nucleation, is the rate-limiting step for the precipitation of dipyridamole. A linear dose-response relationship was found for the mean in vitro duodenal area under concentration-time curves (AUC∞) in the dose range of 25 mg to 100 mg (R(2) = 0.886). This is in agreement with the pharmacokinetic data of dipyridamole reported in the literature. The simulated stomach duodenum model can provide a reliable and discriminative screening tool for exploring the effect of different physiological variables or formulations on the supersaturation/precipitation kinetics of weakly basic drugs with solubility limited absorption. The amount of drug in solution in the duodenal compartment of the SSD correlates to bioavailability for the weakly basic drug, dipyridamole, which has solubility limited absorption and undergoes supersaturation/precipitation.

Functional Outcomes According to the Size of the Gastric Remnant and the Type of Reconstruction Following Distal Gastrectomy for Gastric Cancer: An Investigation Including Total Gastrectomy

In gastric cancer, various methods of gastric resection have been devised according to the location of the primary tumor and the depth of invasion. Functional outcomes were compared among different types of reconstruction following open 2/3- or 4/5 distal gastrectomy for gastric cancer. Resection and reconstruction were performed by one of the following three methods, depending on the depth of cancer invasion and the date of the procedure relative to the introduction of Roux-en-Y reconstruction: distal 2/3 gastrectomy with Roux-en-Y reconstruction (1/3 Roux-en-Y, n = 30); distal 4/5 gastrectomy with Roux-en-Y reconstruction (1/5 Roux-en-Y, n = 15) and distal 2/3 gastrectomy with Billroth I reconstruction (1/3B1, n = 30). Open total gastrectomy with Roux-en-Y reconstruction (total gastrectomy with RY reconstruction, n = 30) was taken as the control procedure. Comparison of postoperative/preoperative body weight ratios and food intake ratios revealed better preservation among patients with a larger remnant stomach (the 1/3 Roux-en-Y and 1/3B1 groups), regardless of the reconstruction. The gastric emptying pattern in larger remnant stomach groups was milder than in the 1/5 Roux-en-Y and total gastrectomy with RY reconstruction groups. Reflux esophagitis was often observed on endoscopy in the 1/3B1 group. Better functional outcomes were observed in patients with a large remnant stomach regardless of the reconstruction.