Gastric emptying in relation to drug absorption

Summary 1. Test meals were given to healthy subjects, and the rate of gastric emptying was assessed from the volumes of the gastric contents recoverable after different periods.2. With test meals of 500 ml. containing a mixture of sodium citrate, sodium bicarbonate, and monocalcium phosphate, the rate of gastric emptying was more rapid than that of water and was largely independent of the concentration of the salts in the meal.3. Neither effervescence of the solutions nor the presence of acetyl-salicylic acid has any notable effect on gastric emptying.4. The influence of the volume of an ingested solution on gastric emptying, based on previous experiments, is outlined.5. These data are considered in relation to the volume and composition of a vehicle for drugs which are intended to reach the small intestine soon after they are taken.The author is grateful to the subjects for their continued co-operation. The dummy tablets, and the active tablets, which are available as Alka Seltzer, were kindly supplied by Miles Laboratories, Inc., Elkhart, Ind.     

Gastric emptying and small-bowel transit rate in the elderly

Gastric emptying of liquid and small bowel transit in a group of elderly patients (mean age 79 years) was studied, with the elderly subjects compared to two groups of young controls. In 14 elderly patients, the initial rate of gastric emptying was significantly higher than in 14 young controls: the five-minute volume was 159 +/- 30 ml (mean +/- SEM) in the elderly patients and 294 +/- 22 ml in the young controls (p less than 0.005). The two groups' gastric emptying rates after five minutes were not significantly different. Small-bowel transit in 15 elderly patients was not significantly different from that found in 15 younger volunteers. These results suggest that gastric homeostatic mechanisms are impaired in the elderly.     

Gastric emptying and orocecal transit time in pregnancy

Purpose. To evaluate the effects of pregnancy on gastrointestinal function, we determined gastric emptying time, orocecal transit time, and fasting gastrointestinal hormone levels (cholecystokinin, gastrin, pancreatic polypeptide, neurotensin) in 11 women with mild dyspeptic symptoms during the first and third trimesters of their pregnancies, and again 4–6 months after delivery. Methods. After the women ingested a disaccharide solution, orocecal transit time was determined by monitoring breath hydrogen concentrations at 10-min intervals, and values were compared with the postpartum value. Ultrasound examinations of gastric emptying were performed during the same intervals. Results. The half-emptying time and the final gastric emptying time did not differ in the first and third trimesters and postpartum, but gastrointestinal transit time was significantly longer in the third trimester of pregnancy than postpartum ([100.0 min (range, 50.5–240.0 min] vs 70.0 min [range, 40.5–240.0 min; P < 0.05]), respectively. Mean plasma pancreatic polypeptide values were lower in the third trimester of pregnancy than postpartum, and a negative correlation was observed between pancreatic polypeptide levels and transit time in the third trimester (r = −0.65; P = 0.0261). The plasma levels of other gastrointestinal hormones did not differ in the various periods studied. Conclusions. Our study shows that, despite evident dyspeptic symptoms, there were no significant alterations in gastric emptying or orocecal transit time during the first trimester of pregnancy. Conversely, in the third trimester, orocecal transit time was significantly longer. Received: October 6, 2000 / Accepted: February 23, 2001     

Effect of tricyclamol on gastric emptying and intestinal transit

Summary The effects of a placebo, 50 mg. dose, and the O.E.D. of Tricyclamol on gastric emptying and intestinal transit of a standard barium mixture and Ewald meal were compared in nine patients with duodenal ulcer. Each patient served as his own control. The medicament was given half an hour prior to the ingestion of the barium mixture and Ewald meal. Serial x-rays of the abdomen were then taken.No significant differences were found in the rate of gastric emptying following the placebo or a 50 mg. dose of Tricyclamol. However, the O.E.D. of Tricyclamol produced a delay in gastric emptying of the barium and Ewald mixture at 1- and 2-hour intervals, but none at the 4-hour period. Thus, the O.E.D. of Tricyclamol, though a multiple of the 50 mg. dose, did not produce excessive delay in gastric emptying of the barium mixture and Ewald meal. However, some but no important delay in the progress of the barium along the intestine was noted after Tricyclamol as compared to that produced by the placebo.The authors wish to thank Dr. James B. Hammond of the Eli Lilly and Co., for the Generous supply of Tricyclamol methylsulfate.     

Gastric emptying in the cat in response to hypertonic solutions and tryptophan

Studies of gastric emptying were made in ten cats and four dogs, each with a gastric fistula. Test meals of 50 ml (cats) and 300 ml (dogs) containing phenol red as a nonabsorbable marker were instilled into the stomach via the gastric fistula and were drained by gravity 25–30 min later. The test meals were water, hypertonic solutions (250–1000 mosmol/kg) of casein hydrolysate, D glucose, mannitol, glycine,l-alanine,d-alanine, -alanine;l- andd-tryptophan andl-phenylalanine in concentrations (osmolalities) ranging from 5 to 100 mM. In the cats, gastric emptying was slowed with increasing osmolality of the test solution, and glucose and mannitol were equipotent but much less effective than glycine or casein hydrolysate. This difference in potencies was not found for these substances in the dogs. Gastric emptying was inhibited by tryptophan in the cats, was stereospecific, and only thel form was effective. This inhibition was not due to the effect of tryptophan on acid secretion. Stereospecificity was not found for the osmoreceptor. Combiningl-tryptophan with another neutral amino acid (l-alanine) inhibited the effect of tryptophan. Phenylalanine in concentrations up to 80 mM had no effect on gastric emptying in the cats. These studies indicate differences between cats and dogs in response to osmotic agents and also show that, like the dog, the cat has a tryptophan receptor.     

Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat

Neuropeptide Y is distributed abundantly not only in the brain, but also in the gastrointestinal tract and suppresses intestinal muscle contraction in isolated muscle preparations. The purpose of the present study was to determine whether centrally administered neuropeptide Y modulated gastric emptying and intestinal transit in conscious rats. Graded doses of neuropeptide Y were administered intracisternally 1 min before ingestion of test meals through an oral tube. Four hours after ingestion of 60 Amberlite pellets, the rats were sacrificed and residual pellets in the stomach and the small intestine segments were counted to calculate the solid meal transit rate. The liquid meal transit rate was calculated 1 hr after 0.07% phenol red ingestion by determining the residual phenol red in the stomach and the small intestine segments. Neuropeptide Y elicited potent suppression of gastric emptying and intestinal transit of both solid and liquid meals. Pretreatment with propranolol antagonized, whereas phentolamine did not affect, the suppressive effect of central neuropeptide Y. Although carbachol blocked the effects of neuropeptide Y, neither atropine nor hexamethonium altered the actions of neuropeptide Y. In conclusions, centrally administered neuropeptide Y strongly inhibited gastrointestinal transit by stimulating a beta-adrenergic pathway.     

Gastric emptying rates of solid food in relation to body size

The relationship of body size to rates of gastric emptying of solid food was investigated in order to obtain data that may allow this variable to be considered when populations of varying size are studied. Rates of gastric emptying were measured using a beef stew meal to which were added pieces of chicken liver tagged with [99mTc]sulfur colloid, and following the passage of the isotope through the gastrointestinal tract with intermittent gamma-imaging. Results showed an inverse linear relationship between gastric emptying rates and body surface area, and between gastric emptying rates and body weight. The variable of body size must be taken into account when measurements of gastric emptying of solid food are measured.     

Effects of progesterone on gastric emptying and intestinal transit in male rats

AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and Pon gastrointestinal motility.METHODS: In order to monitor the gastric emptying andintestinal transit, the SD male rats were intubated via acatheter with normal saline (3 mi/kg) containing Na251 CrO4(0.5 μCi/ml) and 10 % charcoal.OT was dissolved intonormal saline and P was dissolved into 75 % alcohol.RESULTS: Low does of P (1 mg/kg, i. p. ) enhanced thegastric emptying (75 ± 3 %, P＜ 0.05) and high dose of P (5mg/kg, i.p. ) inhibit it (42± 11.2 %, P＜ 0.01). P (1 rog/kg)increased the intestinal transit (4.2 ± 0. 3, P ＜ 0.05) whilethe higher dose ( 10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p. ) inhibited the gastric emptying (23.5 ± 9.8 %, P ＜0.01). The inhibitory effects of P (20 mg/kg) (32± 9.7 %, P＜ 0.05) and OT (0.8 mg/kg) on gastric emptying enhancedeach other when the two chemicals were administratedsimultaneously ( 17 ± 9.4 %, P ＜ 0.01).CONCLUSION: Low dose of P increased Gl motility whilehigh dose of P decreased it. During the later period ofpregnancy, elevated plasma level of OT may also participatein the gastrointestinal inhibition.     

Effects of progesterone on gastric emptying and intestinal transit in male rats

AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility. METHODS: In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3 ml/kg) containing Na(2)(51)CrO(4) (0.5 microCi/ml) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol. RESULTS: Low does of P (1 mg/kg, i.p.) enhanced the gastric emptying (75+/-3%, P<0.05) and high dose of P (5 mg/kg, i.p.) inhibit it (42+/-11.2%, P<0.01). P (1 mg/kg) increased the intestinal transit (4.2+/-0.3, P<0.05) while the higher dose (10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p.) inhibited the gastric emptying (23.5+/-9.8%, P<0.01). The inhibitory effects of P(20 mg/kg) (32+/-9.7%, P<0.05) and OT (0.8 mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17+/-9.4%, P<0.01). CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.     

Gastric emptying of oral rehydration solutions in acute cholera

Gastric emptying of rice powder electrolyte solution and of glucose electrolyte solution was measured by a marker dilution double sampling technique in 14 and in 16 adult patients respectively after intravenous rehydration during an attack of acute cholera. Six patients who received rice powder electrolyte solution and seven who received glucose electrolyte solution re-attended for a repeat study with the same test meal 16 days later, when fully recovered from cholera. No differences in gastric emptying patterns of the two electrolyte solutions were observed, either in the acute or in the recovered patients. Similarly, gastric emptying of both solutions was rapid during acute cholera and comparable to that observed in recovered patients. This study indicates that gastric emptying is not impaired in acute cholera and that the rate of emptying of oral rehydration solutions is adequate to account for their observed clinical efficacy in fast purging patients with acute cholera.     

Gastric emptying and small intestinal mucosal injury in rats.

A technique was developed to produce small intestinal mucosal injury in vivo by perfusing the mid-small intestine of rats with HCl, NaOH, FeSO4, and AgNO3. Three hours following injury, gastric emptying and small intestinal transit were measured by examining the gastrointestinal distribution of a non-absorbable radioisotope which had been placed in the stomach for 1 hour. There was a strong association between the villus injury produced by various concentrations of the injurious agents and the degree of gastric retention. Necrosis of villus tips, as produced by AgNO3, was sufficient to cause marked gastric retention. Injury to the small intestinal mucosa of one parabiotic rat did not produce gastric retention in the partner. It is concluded that injury to small intestinal villi is sufficient to induce gastric retention and that the effect is most likely nerve-mediated.     

Small intestinal transit in the portal hypertensive rat

The purpose of this study was to determine the effects of portal hypertension on gastrointestinal transit. Portal hypertension was induced in a group of 15 rats by the staged portal vein ligation technique. A control group of 15 rats underwent a sham operation. Ten days later, a 51Cr-labeled Krebs' buffer solution was instilled into the duodenum and the distribution or radioactivity along the length of the small intestine was determined after 15, 30, and 60 minutes. Portal hypertension was consistently established in the study group; splenic pulp pressure (mm Hg, mean +/- SD, portal hypertensive vs. control) was 20.0 +/- 3.9 vs. 12.7 +/- 3.9, P less than 0.002. Various measures of intestinal transit revealed delayed transit in the portal hypertensive group. Retention of radioactivity in the most proximal quartile of the intestine was greater [percentage retained (portal hypertensive vs. control) was 57.9 +/- 17.3 vs. 31.2 +/- 15.3, P less than 0.02, 49.1 +/- 15.5 vs. 28.3 +/- 4.8, P = 0.03, and 42.4 +/- 17.6 vs. 29.0 +/- 8.8, P = 0.08, at 15, 30, and 60 minutes, respectively] and the geometric mean of transit was located more proximally (P less than 0.02) at each study interval in the portal hypertension group. It was concluded that portal hypertension is associated with delayed intestinal transit. This abnormality could predispose to bacterial overgrowth and contribute to altered digestion and absorption.     

Gastric emptying of liquids and solids in the portal hypertensive rat

The effects of portal hypertension on gastric motor function were investigated using the rat staged portal vein ligation model. Gastric emptying of liquids and solids was studied separately following meals labeled with 51Cr or 99Tc by whole stomach scintillation counting. Portal hypertension was consistently established in experimental rats (splenic pulp pressure: mean +/- SEM, portal hypertension versus control, 16.8 +/- 0.7 vs 11.8 +/- 0.7 mm Hg, P less than 0.0001). Although liquids were emptied in an exponential manner and solids in a linear fashion, gastric emptying of both meals was more rapid in the experimental rats. Ten minutes after the liquid meal, more than 50% of the meal had emptied from the stomachs of portal hypertensive rats while only one third of the meal had cleared in the control group (P less than 0.02). Gastric emptying of the solid meal was significantly accelerated in experimental rats at 60 and 120 min (percent meal remaining: portal hypertension versus control, 41.9 +/- 4.0 vs 55.4 +/- 3.5 and 21.5 +/- 4.9 vs 32.6 +/- 4.3, P less than 0.05). Stomachs of portal hypertensive animals were heavier (P less than 0.009) and histologic examination revealed submucosal edema. Thus, a possible mechanism of the disrupted gastric motor function in portal hypertension is decreased gastric wall compliance secondary to edema.     

Transforming growth factor-alpha delays gastric emptying and small intestinal transit in suckling rats

Transforming growth factor-alpha (TGF-alpha) is a biologically potent polypeptide detected in the gastrointestinal tract in suckling rats. The major goal of the present study was to test the hypothesis that the administration of TGF-alpha affects gastric emptying and small intestinal transit in suckling rats. Suckling (12-day-old) rats fasted 16 h received rat TGF-alpha subcutaneously (s.c.) or orogastrically in varying doses (0, 0.5, 1.0 microg/rat in 0.1% BSA). Control animals received 0.1% BSA only. Poly R-478 dye was used as a motility marker. Rats were decapitated 45 min after marker administration and the amount of dye in the stomach and the small intestine was measured by spectrophotometry. Subcutaneous administration of TGF-alpha significantly delayed stomach evacuation. In controls, the stomach contained 21.4 +/- 1.4% (mean +/- s(x)) of the Poly R-478 marker, whereas in TGF-alpha treated rats the stomach contained 37.2 +/- 2.8% of the total Poly R-478 dye given to animals. The delaying effect of TGF-alpha was time- and dose-dependent. Small intestinal transit was also significantly delayed. The proximal jejunum of TGF-alpha treated rats contained a 1.4-fold higher amount of marker in comparison with control rats. Orogastrically administered rTGF-alpha did not affect gastric emptying or intestinal transit. In conclusion, s.c. administration of rat TGF-alpha significantly delayed the gastrointestinal motility in vivo in suckling rats.     

Gastric and gallbladder emptying in relation to the secretion of cholecystokinin after a meal in late pregnancy

Gastric and gallbladder emptying was studied in response to a mixed liquid meal in 18 pregnant women and 24 controls without a history of gallbladder or liver disease. Gallbladder and gastric volumes were measured with ultrasound and calculated by the 'sum-of-cylinders' method. The gastric emptying of protein was estimated by nasogastric aspiration in separate groups of controls and pregnant women. In a subgroup of 9 pregnant women and 8 controls, the secretion of cholecystokinin (CCK) was also measured. Neither gastric volume reduction and emptying nor contraction of the gallbladder and CCK secretion after a liquid mixed meal differed significantly between pregnant women and controls. The gallbladder fasting volume and the residual volume after contraction, however, were significantly increased in pregnant women.