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1.
Summary— Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.  相似文献   

2.
To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates.  相似文献   

3.
The quarternary ammonium antimuscarinic drugs propantheline bromide and clidinium bromide, given orally at the usual therapeutic doses, delayed gastric emptying of a swallowed radiolabeled liquid meal as measured by a gamma camera. Delay of emptying was dose dependent. If an identical meal was given by gastric tube, there was no slowing of emptying by propantheline in the group as a whole. Six subjects who emptied the intubated meal more quickly with placebo had slowed emptying after 30 mg propantheline. In five others, intubation alone slowed gastric emptying while the addition of 30 mg propantheline caused a paradoxical acceleration of gastric emptying. Clidinium bromide, 5 mg, delayed gastric emptying to the same extent as 15 mg propantheline bromide without the marked suppression of salivary secretion induced by the latter.  相似文献   

4.
Many previous studies have found that transabdominal ultrasound may allow precise measurement of gastric emptying of liquid meals. However, the clinical use of this technique has been hampered by the limitation that transabdominal ultrasound might not accurately measure gastric emptying of solid meals. It is more important to measure gastric emptying of solids instead of liquids, as gastric emptying of solids is more often delayed than gastric emptying of liquids in gastric motility disorders. Recently, transabdominal ultrasound after oral administration of a cellulose-based gastric contrast agents (TUS-OSCA) has been suggested to be effective in initial screening of gastric lesions. The aim of this study was to explore the accuracy of TUS-OSCA in the evaluation of gastric emptying of a semisolid meal. Twenty healthy young patients (10 males and 10 females aged 25.5?±?2.5 y) were studied. Concurrent measurements of gastric emptying by scintigraphy and TUS-OSCA were performed after ingestion of 350?mL semisolid ultrasound agent labeled with 20 MBq 99mTc-sulfur colloid. There was no significant difference in the overall curves for gastric emptying time between scintigraphy and TUS-OSCA. There was a good correlation between the gastric 50% emptying times determined by scintigraphy (89.4?±?1.8?min) and TUS-OSCA (92.5?±?1.7?min). The correlation coefficient was r?=?0.922 (p?=?0.000). Current results indicate that TUS-OSCA is accurate, and the results are similar to those obtained by scintigraphy for gastric emptying of a semisolid meal.  相似文献   

5.
The effects of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics of pefloxacin in 10 healthy volunteers were investigated. In a randomized crossover design, each subject received an oral dose of 400 mg of pefloxacin either with or without multiple doses of the antacid. The concentrations of pefloxacin and its metabolites in plasma and urine were determined by high-performance liquid chromatography assays. We found that coadministration of magnesium and aluminum hydroxide caused a decrease of levels of pefloxacin in plasma and urine. The area under the plasma concentration-time curve decreased significantly (P < 0.001), suggesting impaired absorption of pefloxacin from the gastrointestinal tract. The relative bioavailability of pefloxacin after the antacid treatment was 44.4% +/- 23.8%, compared with that after a single administration. The underlying mechanism of this drug interaction is the formation of chelate complexes and probably also physical adsorption to the aluminum hydroxide gel. The metabolism of pefloxacin was not altered by the antacid treatment. Renal clearance was found to depend on urinary pH. Terminal half-life was significantly shorter after the antacid treatment, probably because of an increase in nonrenal clearance. In conclusion, pefloxacin should be given at least 2 h before the antacid to ensure sufficient therapeutic efficacy of the quinolone.  相似文献   

6.
This single-blind crossover trial compared the effects of single oral doses of two antacids on esophageal and gastric pH in subjects with heartburn. Gastric and esophageal pH were assessed in 83 subjects from 1 h before to 4 h after a refluxogenic meal. Subjects received two chewable tablets of a high-potency aluminum/magnesium hydroxide [Al(OH)3/Mg(OH)2] formulation (Mylanta Double-Strength(TM)) or a calcium carbonate [CaCO3] formulation (Tums E-X(TM)), or placebo 1 h after the meal. Both antacid formulations significantly increased esophageal pH, as compared with placebo. Onset of action was faster with the Al(OH)3/Mg(OH)2 formulation than with the CaCO3 in 41 subjects, slower in 13 subjects, and identical in 29 subjects. Area under the esophageal pH--time curves after dosing were significantly greater for Al(OH)3/Mg(OH)2 than for CaCO3 (p < 0.05) and significantly greater for CaCO3 than for placebo (p < 0.05). The duration of Al(OH)3/Mg(OH)2 action in the esophagus was 82 min and 60 min for CaCO3 (p < 0.05). In the stomach, only Al(OH)3/Mg(OH)2 increased gastric pH compared with placebo. After ingestion of calcium carbonate, gastric pH usually remained at or below placebo values, a finding consistent with a calcium carbonate-induced "acid rebound." The duration of Al(OH)3/Mg(OH)2 action in the stomach was 26 min. These findings demonstrate the efficacy and relative superiority of this particular aluminum/magnesium hydroxide formulation compared with the calcium carbonate preparation at increasing esophageal and gastric pH. However, the magnitude and duration of action of both antacids on esophageal pH, in contrast to minimal effects on gastric pH, suggest strongly that the lower esophagus is the primary site of antacid activity in relief of heartburn.  相似文献   

7.
BACKGROUND: Acute hyperglycemia has been associated with delayed gastric emptying of solid foods in healthy control subjects. Erythromycin has been found to be a gastrointestinal prokinetic agent in humans. We examined whether acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of a solid meal after a fasted state in healthy subjects. METHODS: Twelve healthy subjects ate standard solid meals that had been radiolabeled. Gastric emptying was measured by scintigraphy during normoglycemia (5-8.9 mmol/L glucose) and hyperglycemia induced by intravenous glucose (16-19 mmol/L glucose) after administration of placebo or 200 mg of erythromycin intravenously. Emptying was measured randomly on 4 different days. RESULTS: Administration of erythromycin during normoglycemia or induced hyperglycemia compared with placebo accelerated the gastric emptying of the solid meal but did not completely normalize the delay caused by hyperglycemia versus normoglycemia (p < 0.001). In both conditions, erythromycin versus placebo significantly reduced the lag-phase duration (9.7 +/- 2.3 min and 22.0 +/- 3.9 min vs. 38.3 +/- 5.7 min and 49.5 +/- 6.0 min, respectively; p < 0.001), gastric emptying of the half meal (39.2 +/- 4.0 min and 52.0 +/- 7.1 min vs. 75.7 +/- 11.8 min and 94.0 +/- 13.4 min, respectively; p < 0.001), and the percentage of meal retained in the stomach 120 min postprandially (p < 0.001). CONCLUSION: The erythromycin-induced acceleration effect on gastric emptying was related to the plasma glucose level. Hyperglycemia might have chosen a cholinergic antagonist pathway that delayed gastric emptying of solids. Even though induced hyperglycemia inhibited gastric emptying, erythromycin accelerated the gastric emptying rate through two distinct pathways: cholinergic and noncholinergic.  相似文献   

8.
BACKGROUND: Noninvasive breath tests may have significant utility for the measurement of gastric emptying in mice, but the tests' sensitivity for detection of changes in gastric emptying has not been evaluated. MATERIALS AND METHODS: Hydroxypropyl methyl cellulose was incorporated into a liquid meal to delay gastric emptying, and mice were injected with erythromycin to accelerate emptying of a liquid or solid meal. All test meals were labelled with (13)C-acetic acid or (13)C-octanoic acid. Breath samples collected at intervals were analysed for (13)CO(2) content, and gastric emptying rates were calculated from the resultant (13)CO(2) excretion curves. RESULTS: As predicted, hydroxypropyl methyl cellulose slowed emptying compared with water (14.21 +/- 0.94 min vs. 9.17 +/- 0.47 min, P < 0.001), while erythromycin treatment accelerated emptying of liquids (10.96 +/- 0.78 min vs. 16.41 +/- 1.94 min, P < 0.05) and solids (108.81 +/- 18.06 vs. 157.95 +/- 12.01 min, P < 0.05) compared with the saline injected controls. CONCLUSIONS: These data indicate that in mice the breath test is sensitive enough to detect differences in gastric emptying induced by meal composition and pharmacological agents. Noninvasive measurement of gastric emptying in mice will be useful as a method to evaluate the effect of nutrients or drugs on the motility of the gastrointestinal tract.  相似文献   

9.
Predictors of delayed gastric emptying in diabetes.   总被引:17,自引:0,他引:17  
OBJECTIVE: To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS: The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 +/- 3.2 vs. 50.2 +/- 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 +/- 1.7 vs. 16.0 +/- 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS: We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.  相似文献   

10.
Gamma scintigraphy was used to measure the gastric emptying rates of three test meals in human volunteers. Emptying rates were determined for solid and liquid materials alone, and for liquid in the presence of solid material. It was shown that the emptying of solids from the stomach was significantly slower than that of liquid, whether liquid alone or liquid in the presence of solid material. It was concluded from these results that, in the case of a solid test meal from which radio-label could be eluted, the free label would empty considerably faster than the remaining solid material. The emptying rate observed scintigraphically would not, therefore, be a true estimate of the solid emptying rate.  相似文献   

11.
This double-blind crossover trial compared the postmeal effects of single doses of liquid antacids on esophageal and gastric pH in patients with a history of heartburn. Treatment consisted of one of two antacids containing the same active components---aluminum and magnesium hydroxide---but different in vitro acid-neutralizing capacities (ANCs). The pH was assessed continually from 1 h before a refluxogenic meal to 4 h after its completion in 24 subjects who received 20 ml of Mylanta((R)) Double Strength (MYL-20: ANC = 101.6 mEq), 20 or 30 ml of Extra-Strength Maalox((R)) Plus (MA-20, MA-30: ANC = 116.2 and 174.3 mEq, respectively), or placebo (ANC = 0) in random order. Esophageal pH increased rapidly and significantly (p < 0.05) to peak values of 7.0--7.4 with antacid. The increase in mean esophageal pH values was significantly higher (p < 0.05) than placebo for 30 min with MA-20 and for at least 70 min with MYL-20 and MA-30. In contrast, gastric pH rose slowly to mean peaks of 2.9--3.1 with antacid. During this interval, only MYL-20 was associated with significant improvements (p < 0.05 versus placebo) in total number of reflux episodes and total time that esophageal pH measured >4. Thus, ANC alone is not a useful guide in predicting in vivo antacid behavior, as in this study where the antacid dose with the lowest ANC demonstrated a duration of action as long or longer than that of antacid doses with higher ANC values. The rapid, prolonged increases in esophageal pH that preceded modest changes in gastric pH strongly suggest that the lower esophagus is the primary site of antacid action for heartburn relief.  相似文献   

12.
A new approach to increasing tolerance to oral aminophylline therapy is reported. It consists of giving, together with aminophylline, a nonabsorbable, sodium-free antacid in the form of aluminum hydroxide gel. This mixture greatly reduces the irritating effect of aminophylline on the gastrointestinal tract without interfering with its absorption. It permits the administration of larger doses of aminophylline for therapeutic purposes.  相似文献   

13.
To study gastric emptying and secretion, liquid meals of 10% glucose lasting 15 and 30 min, and physiological saline meals lasting 30 min, all containing phenol red as a gastric nonabsorbable marker, were given to postvagotomy patients with Finney or Heineke-Mikulicz pyloroplasties. No differences in emptying were found. A small but statistically greater amount of acid was found in the stomach with the 15-min glucose meal after Heineke-Mikulicz pyloroplasty. This represented greater acid secretion into glucose meals generally after Heineke-Mikulicz pyloroplasties, because of the larger volume contained in the stomach at 15 min. 15-min glucose meal acid secretion correlated with basal acid concentration but not with insulin-stimulated gastric acid output. The small excess of acid in the Heineke-Mikulicz group's 15-min glucose meals may represent a small, maintained excess of gastric acid in this group detected only in the brief glucose meals due to rapid and erratic gastric emptying of liquids after vagotomy.  相似文献   

14.
BACKGROUND: Delayed gastric emptying is a common disorder among patients with end-stage renal failure (ESRF). Pyloric relaxation, a major determinant of gastric emptying, is a nitric oxide (NO)-mediated process. NO-induced smooth muscle relaxation is mediated through its second messenger cyclic guanosine monophosphate, which is broken by tissue phosphodiesterases (PDEs). Thus the inhibition of cyclic guanosine monophosphate breakdown by PDE inhibitors can potentiate NO-mediated responses and facilitate pyloric relaxation. In an animal model of diabetes mellitus, treatment with sildenafil (a PDE-5 inhibitor) restored NO-mediated pyloric relaxation and improved gastric emptying. The aim of our study was to examine the hypothesis that sildenafil may improve gastric emptying in patients with ESRF and symptoms of gastric paresis. METHODS: We studied 12 patients with ESRF (6 men; age range, 54-80 years; 5 with diabetic nephropathy; 4 +/- 1 years receiving long-term renal replacement therapy) after either placebo or a 25-mg tablet of sildenafil (Viagra; Pfizer Inc). Gastric emptying of a solid meal (one medium-sized fried egg mixed with 37 MBq [1 mCi] technetium Tc 99m phytate plus 1 slice of bread and 150 mL of water at the end of the meal) was assessed 1 hour after dosing by use of a single-headed camera. Images were acquired every 30 seconds for 90 minutes immediately after patients ate. RESULTS: The gastric emptying rate was decreased at baseline (after placebo), to 33% +/- 6% (normal, > or =50%). Treatment with sildenafil had no effect on gastric emptying rates after 90 minutes (from 33% +/- 6% after placebo to 30% +/- 6% after sildenafil, P =.9). CONCLUSIONS: Sildenafil did not improve gastric emptying in patients with ESRF and gastric paresis. Sildenafil may have opposing effects on gastric peristalsis (causing gastric relaxation) compared with its effects on pyloric relaxation. Studies combining sildenafil with prokinetic drugs are of interest.  相似文献   

15.
The effect of glucagon (143 nmol i.v. bolus followed by 430 nmol infused at a constant rate over 90 min) vs placebo (normal saline) on gastric emptying was examined in a blind randomized study in eight healthy males. The gastric emptying of a radiolabelled solid meal was measured with the use of a gamma camera. Glucagon elicited a pronounced delay in gastric emptying in all subjects examined--mean gastric transit time MTT90 glucagon 44.2 +/- 0.22 min vs placebo 38.6 +/- 0.74 min, p less than 0.001.  相似文献   

16.
The aim of this study was to determine the effect of 1 week of antacid dosing on the aspirin-induced potential differences (PDs) across the gastric mucosa. The study design was double blind and randomized with crossover. Ten healthy subjects received aluminum hydroxide gel, 8 gm t.i.d., or placebo for 1 week. They then received 1 gm aspirin after an overnight fast and the PD across the mucosa was measured. Baseline potentials were the same before both treatment periods. Antacids reduced the aspirin-induced PDs. The mean (+/- SD) maximal PD was 27.4 +/- 1.7 mV with placebo vs. 10.7 +/- 2.2 mV with antacids (p less than 0.001). Recovery time was 65.5 +/- 5.2 minutes with placebo vs. 29.0 +/- 6.7 minutes with antacids (p less than 0.001). These results suggest the effect is due to a longer-term cytoprotective property of antacids rather than to acid-neutralizing activity.  相似文献   

17.
Intestinal folic acid transport is a saturable process with a pH optimum of 5.5 to 6.0. Because of the possible effects of antacids and acid-lowering drugs on the pH of the proximal small intestine, the influence of these drugs on folic acid absorption was studied by using tritium-labeled pteroylmonoglutamic acid (PGA) in 30 subjects (21 women, nine men) of 56 to 89 years of age. Both cimetidine and an antacid containing aluminum and magnesium hydroxide reduced folate absorption from a liquid formula meal (p less than 0.01, p less than 0.001, respectively). Although ranitidine also caused a fall in folic acid absorption from the liquid meal, the change was not statistically significantly different from when PGA was given with the meal alone. Both histamine receptor antagonists tended to maintain a high intraluminal pH in the proximal small intestine after meals, which in part could explain the inhibition of folate absorption. However, neither drug was found to chemically interact with folic acid, and neither drug inhibited the dihydrofolate reductase. The antacid was found to precipitate folic acid at a pH of greater than 4.0, thus removing it from the aqueous phase. This appears to be the explanation for the lowered folate absorption in the presence of antacid. Although the effects of these drugs on reducing folic acid absorption were relatively small, such reductions could become clinically significant in chronic antacid or H2 receptor antagonist use or intensive antacid or H2 receptor antagonist use by individuals eating diets that are marginal in folate content.  相似文献   

18.
Summary. Oesophageal emptying of solids and liquids has been assessed in normal subjects using radionuclide techniques. The solid bolus comprised a 10 g disc of cooked minced beef which was labelled with 160 μCi; 99m Tc macro-aggregated albumin (MAA). The liquid bolus consisted of 15 ml of water labelled with 300 μCi; 99m Tc. Studies were performed in the upright and supine positions and repeated after ingestion of 30 ml of 0.1m HC1 diluted to pH 1.6. Solid and liquid assessments were performed separately with a scintillation camera positioned posteriorly. Subjects were instructed to swallow at the commencement of the test and at 15 s intervals subsequently, until the bolus entered the stomach. Oesophageal emptying in the supine position was significantly slower than emptying in the upright position. This was true for both solid and liquid emptying, in the neutral and in the acidified oesophagus. Emptying of a solid bolus did not appear to be influenced by oesophageal pH. However, emptying of a liquid bolus was significantly slower when the oesophageal pH was acid, for both the supine and upright positions. We conclude that the supine posture delays both liquid and solid oesophageal emptying. The presence of acid in the oesophagus at a pH of 1.6 delayed liquid emptying, but not solid emptying, from the oesophagus.  相似文献   

19.
The present study shows that a single oral recommended dose of propantheline bromide normally doubles the mean gastric half-emptying time in man. In a prospective, double-blind, randomized crossover design 13 normal subjects were given 30 mg propantheline or placebo 90 min before taking a 113m-indium-labeled liquid test meal, the volume of which was adjusted to body weight. The disappearance of radioisotope from the area of the stomach was determined by external gamma counting. After placebo the mean half-emptying time was 68 min and after propantheline it was 135 min (p less than 0.005). Although salivary flow decreased and pulse rate increased there were no visual disturbances. In studies already reported maximally tolerated oral doses of quaternary ammonium anticholinergic drugs have not consistently retarded gastric emptying in man.  相似文献   

20.
It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.  相似文献   

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