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1.
OBJECTIVE: To develop a model based on mean residence time for better understanding the effect of grapefruit juice on the metabolism of nifedipine (NIF). MATERIAL AND METHODS: Sixteen healthy volunteers from an urban population were included. For each trial, the subjects drank water, fresh grapefruit juice or bottled grapefruit juice. Thirty minutes later, the subjects took a 10 mg capsule of NIF, orally. Plasma concentration of NIF was measured and the kinetic parameters were calculated with a non-compartmental model. RESULTS: Grapefruit juice increased the bioavailability of NIF, but did not significantly reduce the drug's metabolism as shown by the approximately constant metabolite to parent drug AUC ratio (P = 0.948). There was no significant increase in the amount of non-metabolized drug absorbed during first-pass: 0.12 and 0.16 (P = 0.470) without and with grapefruit juices respectively. There was an increase in the relative bioavailability (P = 0.039) and the apparent volume of distribution (Vdm) (P = 0.025) of dehydronifedipine with grapefruit co-administration. A second peak was also observed in the NIF plasma-concentration profile when the drug is co-administered with grapefruit juice. Therefore, the most likely explanation for the double peak phenomenon is a delay in gastric emptying (+32 min with grapefruit juice) caused by the pH of grapefruit juice. CONCLUSION: This study shows that grapefruit juice interferes with the metabolism of NIF by inhibiting NIF metabolism and slowing down the rate of gastric emptying. This study also confirms that the metabolic inhibition is not a first pass effect, but is a secondary oxidative step.  相似文献   

2.
A prospective study was undertaken to determine if gastric motility and emptying are altered by the ingestion of overdoses of tricyclic antidepressants, acetaminophen, opioid-acetaminophen mixtures, carbamazepine or phenytoin. Gastric scintigraphy was used to measure gastric emptying half-time and assess gastric motility in 104 patients at initial presentation and again at follow-up (n = 85). Patients were imaged for 5 hours after being given 20 MBq of 99mTc tin colloid to drink. Drug serum levels were measured on all patients at initial presentation and at follow-up. We observed markedly prolonged gastric emptying half-times and severe hypomotility at initial presentation compared with follow-up in the vast majority of patients, except for a small group of patients with phenytoin poisoning. Twelve patients had gastric emptying half-times of over 300 minutes, a further 14 had half-times of over 200 minutes and 21 others had half-times of over 120 minutes. Poisoning is associated with hypomotility and a marked delay in gastric emptying that could influence the clinical course and patient management. These abnormalities may not be due to a direct effect of the ingested drug and factors such as stress may play a role.  相似文献   

3.
Abstract. The relationship between calcium absorption and gastric emptying and the precision of measurement of fractional calcium absorption using a single isotope technique were evaluated in 14 normal postmenopausal women (age range 61–72 years). On two occasions separated by between 5 and 15 days, each subject was given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood samples were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption of the drink, and gastric emptying (GE) was monitored with a gamma camera. Fractional calcium absorption in the first hour (α6) was calculated from the blood samples obtained at 15, 30, 45, 60, 90 and 120 min. An absorption rate was also derived from the 60 min sample using only a calibration curve (α1). There were close correlations between radiocalcium absorption on the two study days ( r = 0.89, P < 0.001 for both α1 and α6) and between α1 and α6 ( r = 0.93, P < 0.001). Plasma paracetamol concentrations at 15 min were directly related to the early phase of GE ( r = 0.42, P < 0.05). In contrast, calcium absorption was inversely related to GE ( r — 0.45, P < 0.05). We conclude that radiocalcium absorption is not greatly influenced by gastric emptying rate and that the single blood sample procedure has similar precision to the six-blood sample test.  相似文献   

4.
Abstract. Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through dis-inhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by realtime ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 ± 6.9 vs. 21.6 ± l.7mL, P <0.02), larger residual volume (12.3 ± 1.8 vs. 4.0 ± 0.5ml, P < 0.0006) and slower emptying time ( T /2: 33 ± 2 vs. 21 ± 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 ± 578 vs. 7908 ± 491 % 120min-1, P <0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.  相似文献   

5.
OBJECTIVES: Amylin is a novel 37 amino acid that is secreted together with insulin from the pancreas in response to enteral nutrient intake. As a potent inhibitor of gastric motility it plays an important role in the control of carbohydrate absorption. In this study we aimed to determine the relationship between amylin levels and gastric emptying in critically ill children. DESIGN: Prospective interventional study. SETTING: Tertiary paediatric intensive care unit. PATIENTS: Twenty-three patients were studied following admission to a paediatric intensive care unit. The median age (25th-75th centiles) was 5.8 years (1.5-11.6) and weight 20 kg (12.8-47.5). INTERVENTIONS: Patients were defined as feed-intolerant on the basis of gastric residual volume greater than 125% 4 h after a feed challenge. Three objective measures of gastric emptying were then calculated from a 6 h paracetamol absorption test. Blood glucose, serum insulin and amylin levels were averaged across the paracetamol absorption test period. MEASUREMENTS AND RESULTS: Eight patients were classified as feed-intolerant (nTOL) and 15 as feed-tolerant (TOL) [median gastric residual volumes 321% (261-495) and 4% (0-6), respectively]. Gastric emptying was delayed in the feed-intolerant group as assessed by all paracetamol absorption test parameters ( p< or =0.01). The median serum amylin concentration was significantly higher in the feed-intolerant group [nTOL 47.0 (37.7-54.8) versus TOL 22.7 (13.6-26.7) pmol/l, p<0.0001]. A positive correlation between serum amylin and insulin was observed ( r=0.46, p=0.02) but not between amylin and glucose ( r=0.25, p=0.23). CONCLUSIONS: The use of gastric residual volumes to define feed intolerance is justified in critically ill children. High serum amylin levels are associated with delayed gastric emptying in these patients. The correlation between serum amylin and insulin levels indicates a degree of preservation of pancreatic hormonal co-release.  相似文献   

6.
Abstract. We have used the forearm model to study protein metabolism in six normal healthy subjects in the fed state using L-[1 –13C, 15N]-leucine as the substrate tracer.
Deep venous and arterialized venous blood samples from the forearm were collected at 10-min intervals 2±5 h into a primed-continuous infusion of the dilabelled tracer. Arterialized venous blood was obtained using a 'hot-box' technique and forearm blood flow was measured by mercury strain-gauge plethysmography.
The concentration and isotope enrichment of leucine and its metabolites, α-ketoisocaproic acid and CO2, in deep venous and arterialized venous blood were measured by gas chromatography-mass spectrometry and isotope ratio-mass spectrometry.
The rates of leucine deamination and reamination were 388 ± 24 (mean ± SEM) and 330 ± 23 nmol (100 ml)-1 min-1 respectively, whilst protein synthesis and breakdown rates were 127 ± 11 and 87 ± 10 nmol (100 ml)-1 min-1 respectively across the forearm in the fed state. We have demonstrated that the use of doubly labelled leucine as tracer and application of the mathematical model developed in this study, permits the comprehensive quantification of leucine kinetics including protein breakdown.  相似文献   

7.
Abstract. A gastric antigen with enzymatic activity (VI A) was purified by gel filtration and anion exchange chromatography from gastric juice. Rabbits were immunized with the pure antigen and produced highly specific precipitating antibodies. The specific antisera were subsequently used as immunoadsorbents for a one-step purification procedure. The immunoadsorption technique yielded a pure antigen fraction. When gastric mucosa or gastric juice neutralized in vivo were used as starting materials instead of acid gastric juice, two serum proteins, IgG and albumin, were eluted with the antigen. During gel filtration two different molecular forms of the antigen were observed. The antigen obtained for gastric juice had a molecular weight of 140000, whereas the antigen from gastric mucosa had a molecular weight of approximately 70000. The antigen obtained by different purification procedures showed immunological identity. Preliminary characterization studies showed that the antigen is a heat- and acid-stable antigen with the enzymatic activity of a non-specific carboxyl esterase with a pH optimum between pH 6.4 and 6.8.  相似文献   

8.
目的:观察中脏腑急性期合并应激性上消化道出血患者血清胃肠激素动态变化及胃液酸度、胃排空变化,以探讨中脏腑合并应激性胃黏膜病变的发病环节。方法:中脏腑急性期患者(GCS评分6-12分)20例,均于发病12小时内合并上消化道出血;采用放射免疫分析法,分别于发病后第1日(24小时内)、第4日(72-96小时内)测定其血浆胃动素(MTL)、生长抑素(SS)、血清胃泌素(GAS)水平,并于发病24小时内留置胃管动态观察胃液pH及胃排空情况。结果:与正常对照组比较:患者组发病当日(24小时内)胃动素显著增高(P<0.05),生长抑素显著降低(P>0.05);其中17例患者胃排空延迟。发病第4日胃动素仍显著增高(P<0.01),生长抑素仍显著降低(P<0.05),胃泌素显著增高(P<0.01)。结论:中脏腑急性期合并上消化道出血与胃动素、生长抑素水平的变化密切相关;胃泌素及胃酸量的变化可能并非主要的因素。  相似文献   

9.
Gelox antacid activity has been evaluated in a dynamic procedure by using the "artificial stomach" model that mimics both gastric fluxes, gastric secretion and gastric emptying. At time 0, the gastric reservoir has been filled by 100 ml of 0.1 N hydrochloric acid solution without or with protein, or by 100 ml of human gastric juice (pH 1.1). Gastric secretion was simulated by a constant 3 ml/min flux of HCl solution or of human gastric juice. Gastric emptying fluxes varied from 1.5 to 4.5 ml/min. Gelox addition to 100 ml of 0.1 N HCl or of human gastric juice induced 1) a pH-rise from 1.0 to 4.5-5.8, 2) a buffering capacity close to pH 3.6-4.0 and 3) the consumption of an acid amount between 25 and 50 mmol according to emptying fluxes, for recovering initial pH. In a mixture of HCl 0.1 N and protein extract 1 or 5%, Gelox induced 1) a pH-rise related to the protein concentrations, 2) a buffering capacity close to pH 3.2-3.9 when 1% protein extract has been used, and close to pH 5.0-5.9 with 5% protein extract and 3) a greater acid consumption with 1% than with 5% protein extract. For both protein concentrations, the resistance for recovering the initial pH, expressed as the amount of consumed mmol H+, was therefore less than the sum of individual capacities of proteins and Gelox.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
Amoxicillin when administered with gastric acid suppressors has been shown to be effective in eradication of Helicobacter pylori in 50 to 80% of subjects. The aim of this investigator-blind crossover study was to determine if gastric mucosal amoxicillin uptake was affected by increasing gastric juice pH. Fifteen male subjects (7 H. pylori positive and 8 H. pylori negative) were randomized to receive 150 mg of ranitidine twice a day, 300 mg of ranitidine twice a day, or no drug for 2 days prior to upper endoscopy. The last dose of ranitidine was given 60 min prior to upper endoscopy, and amoxicillin (500 mg) was given 30 min prior to upper endoscopy. The amoxicillin concentrations in mucosal biopsy samples, gastric juice, and serum were determined by a standard microbiological bioassay technique. Mean amoxicillin levels were greater in samples of antrum, fundus, and duodenum for volunteers who received no ranitidine than in those receiving 300 mg of ranitidine (P < 0.05) and those receiving 150 mg of ranitidine (P < 0.05 except for fundus). Amoxicillin levels in the antrum, fundus, and duodenum were negatively correlated with gastric juice pH (P < 0.005 for antrum; P < 0.001 for fundus and duodenum). There was no correlation between gastric juice pH and amoxicillin levels in either gastric juice or serum. The amoxicillin concentration in gastric juice was significantly higher with 300 mg of ranitidine than with no ranitidine (P < 0.05). Thus, lower gastric juice pH is associated with a higher rate of mucosal uptake of amoxicillin.  相似文献   

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