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1.
In animal and human studies, the gastric emptying of large (greater than 1 mm) indigestible solids is due to the activity of the interdigestive migrating myoelectric complex. The gastric residence time (GRT) of an orally administered, nondigestible, pH-sensitive, radiotelemetric device (Heidelberg capsule) was evaluated in three studies in healthy volunteers. In 6 subjects, the GRT of the Heidelberg capsule was compared with the half-emptying time (t1/2) of diethylenetriaminepentaacetic acid labeled with technetium 99m after a 4-ml/kg liquid fatty meal. The mean (+/-SD) GRT (4.3 +/- 1.4 h) was significantly (p less than 0.001) longer than the mean t1/2 (1.1 +/- 0.3 h); the GRT was prolonged compared with the t1/2 in each subject. In a randomized, crossover trial in 10 subjects, frequent feeding caused a dramatic prolongation in mean GRT of the capsule compared with the fasting state (greater than 14.5 vs. 0.5 h, p less than 0.005). In another crossover study in 6 subjects, the GRT of the capsule was evaluated after an overnight fast, a standard breakfast including solid food, and a liquid meal (i.e., 200 ml of diluted light cream). The mean GRT was 2.6 +/- 0.9 h after the liquid meal vs. 1.2 +/- 0.8 h after fasting (p less than 0.025). The mean GRT after the breakfast was 4.8 +/- 1.5 h, which was significantly greater than that after fasting (p less than 0.001) and after the liquid meal (p less than 0.01). These data suggest that the GRT of the Heidelberg capsule is a marker of the interdigestive migrating myoelectric complex in humans, the interdigestive migrating myoelectric complex can be markedly delayed by frequent feedings with solids, and the interdigestive migrating myoelectric complex is delayed by both liquid and solid meals.  相似文献   
2.
An easy, analytically sound fluoroenzymatic assay for angiotensin converting enzyme (ACE) inhibitors is described. Drug samples and standards are extracted with methanol and evaporated to dryness. Drug residues are then incubated with the substrate N-benzyloxycarbonyl-phenyllanyl-l-histidyl-leucine and human plasma ACE at 37 degrees C, pH 7.65, for 1 h. Fluorescence of the o-phthaldialdehyde derivatized product is measured at wavelengths of 365 nm (excitation) and 490 nm (emission). A computer program converts fluorescence to percent of ACE activity inhibited and correlates this percent inhibition with drug concentration. The ester prodrug enalapril (MK-421) was measurable at levels of a 1 ng ml(-1) in serum after base hydrolysis to enalaprilat. Lowest reliable detection limits for enalaprilat (MK-422) and lisinopril (MK-521) in serum were 0.7 ng ml(-1). This method is easily adapted to most other ACE inhibitors, is well suited to automation and avoids the use of radioactivity.  相似文献   
3.
A healthy society is the foundation of development in every country, and one way to achieve a healthy society is to promote healthy nutrition. An unbalanced diet is one of the leading causes of noncommunicable diseases globally. If food was correctly selected and correctly consumed, both the problems of overeating and lack of nutrition could be largely solved while also decreasing public health costs. Interventions such as presenting necessary information and warning labels would help consumers make better food choices. Hence, providing nutritional information to consumers becomes essential. The present study investigates the importance of nutrition information labels on consumers’ preferences by estimating their willingness to pay for features and information provided by a dietary software program (app). An application can easily display the information to the consumers and help them make informed food choices. A discrete choice experiment investigated consumers’ preferences and willingness to pay to receive nutritional information. Mixed multinomial logit and latent class analysis were applied. The results showed the existence of heterogeneity in consumer preferences for different nutritional information provided by the application. Consumers are willing to pay more for salt and fat alerts. The results of this study allow for the analysis of consumers’ interest in nutritional information. Such results are essential for the industry for future investments in similar applications that potentially could help consumers make better informed choices.  相似文献   
4.
The tablet form of amiodarone is indicated for the treatment of recurrent ventricular fibrillation or hemodynamically unstable ventricular tachycardia. It is recommended that the tablet be taken with meals in cases of gastrointestinal intolerance. However, the effect of food on its bioavailability is unknown. The primary objective of this study was to determine the effect of food on the bioavailability of amiodarone. This was a 2-period crossover study conducted in 30 healthy male subjects. Subjects were randomly assigned to 1 of 2 sequences in which the following 2 treatments were administered: (1) a single-dose of amiodarone (three 200-mg Cordarone tablets) after an overnight fast, and (2) the same dose immediately after a standard high-fat breakfast. Plasma concentrations of amiodarone and desethylamiodarone (DEA) were measured for 6 weeks after each dose. Food enhanced the extent of absorption, resulting in a peak concentration (Cmax) and area under the curve (AUCT) 3.8 and 2.4 times the respective values under fasting conditions. Food also significantly increased the rate of absorption, reducing the time (tmax) to Cmax from 7.1 to 4.5 hours. The effect of food on DEA levels was significant but less pronounced. An in vitro dissolution study confirmed a marked difference between amiodarone release under simulated fed and fasting conditions. Thus, food significantly enhances both the rate and extent of absorption of amiodarone, which is attributed partially to the effect of food on drug release from its formulation. Therefore, it is recommended that amiodarone tablets be taken consistently with meals.  相似文献   
5.
6.
The objectives of the present study were to evaluate gastric and small bowel transit times of an indigestible solid matrix and to characterize the specific changes in intraluminal pH as a function of transit time through the gastrointestinal tract. Particular attention was paid to the lag time at the ileocecal junction. A Heidelberg capsule (HC), labeled with 10 µCi Indium-111, was given orally to six healthy male subjects 15 min after oral ingestion of 100 µCi of 99mTc-sulfur colloid as a liquid fatty meal (4 ml/kg). Intraluminal pH was monitored continuously via the HC. Gastric and small bowel transit of the radionuclides was monitored via external scintigraphy at 0.5-hr intervals. Gastric residence times (GRT) of the HC ranged from 2.8 to 4.8 hr, with a mean (±SD) of 3.6 ± 0.8 hr. These values were independent of the individual's weight, height, or body surface area. Small bowel transit times of the HC ranged from 2.8 to >5.5 hr, which were consistent with the reported values of 3 to 5 hr. The lag times of the HC at ileocecal junction ranged from 0.8 to >2.5 hr. The presence of the lag times at the ileocecal junction in all subjects confirmed that it acts as a valve or sphincter. Mouth-to-cecum transit times of the HC occurred within 9.0 hr in 50% of the subjects. In general, following a sharp rise upon pyloric passage of HC the pH dropped slightly but then increased linearly throughout the small intestine. The mean duodenal pH was 5.8 ± 0.8 and the pH at the ileocecal junction ranged from 6.5 to 8.5, with a mean of 7.3 ± 0.7. Passage through the ileocecal junction was associated with a 0.5- to 1.0-unit rise in pH in three subjects who exhibited passage of the HC into the large bowel within the study period. The present data may have implications in the designing of more effective dosage forms with specific delivery to proximal or distal small bowel regions.  相似文献   
7.
Dimethyl sulfoxide (DMSO) suppresses conversion of the prodrug sulindac to its bioactive sulfide metabolite (SD) by competitively inhibiting sulfoxide reductase. During continuous iv infusions of sulindac (1 mg/kg X h), plasma concentrations of SD at steady-state equilibrium were 80% lower when DMSO was infused concomitantly at 0.34 ml/kg X h, whereas sulindac plasma concentrations were not significantly affected by DMSO. Dermal application and intragastric administration of DMSO also inhibited SD accumulation in plasma. DMSO was only a weak inhibitor of SD oxidation in vitro and did not affect the rate of SD elimination in vivo. In contrast, dimethyl sulfide, a metabolite of DMSO, was a potent inhibitor of SD oxidase in vitro. These data suggest that DMSO can inhibit bioactivation and, hence, the antiinflammatory effects of sulindac.  相似文献   
8.
The relationship between variations in the gastric residence time and the absorption of procainamide from a waxed matrix, sustained-release tablet was evaluated in a repeated-measures study conducted in eight healthy men. Subjects received sustained-release procainamide together with a Heidelberg capsule, alone and with food. Blood and urine samples were collected for up to 24 hours before and after gastric emptying of the Heidelberg capsule for procainamide and N-acetylprocainamide concentration determinations. The gastric residence time of the Heidelberg capsule was prolonged by food (median 3.5 [range 1.5 to 10.0] vs. 1.0 [range 0.5 to 2.5] hours; P less than 0.02). No significant differences (median [range]; fasting vs. fed) in procainamide lag time (0.5 [0.5 to 1.0] vs. 0.5 [0.5 to 1.5] hours) or time at which peak procainamide plasma concentrations occurred (2.9 [1.0 to 4.3] vs. 2.8 [2.0 to 6.0] hours) were evident with feeding. Slight increases in procainamide AUC and peak concentrations occurred with feeding. No alteration in the extent of urinary excretion of procainamide or N-acetylprocainamide occurred with feeding. Thus food did not influence the absorption of sustained-release procainamide despite apparent prolonged gastric retention.  相似文献   
9.
The single-dose pharmacokinetics of the antifungal agent SCH 39304 (Schering-Plough Corp., Kenilworth, NJ) were assessed alone and in combination with antacid and cimetidine. On three separate occasions nine healthy men received a single oral 50 mg dose of SCH 39304 either alone, with 60 mL antacid, or with oral cimetidine 300 mg four times a day for 4 days. Concomitant antacid or cimetidine administration had no significant effect on any of the SCH 39304 pharmacokinetic parameters studied. The oral absorption of SCH 39304, as assessed by the area under the plasma concentration-time curve (AUC) and the amount of drug recovered unchanged in the urine, was not affected by either antacid or cimetidine. The AUC0-1 for the drug given alone was 80.5 +/- 15.8 micrograms.hr/mL, compared to 81.4 +/- 12.7 and 79.7 +/- 9.6 micrograms.hr/mL with concomitant antacid and cimetidine, respectively. The amount of drug excreted in the urine (Ae0-1) was 22.7 +/- 5.1, 24.2 +/- 9.2, and 23.6 +/- 7.6 mg when the drug was given alone, with antacid, and with cimetidine, respectively. Antacid coadministration delayed absorption as evidenced by an increase in the tmax in 7 out of 9 subjects, although this did not reach statistical significance (P = .082, Wilcoxon test). We conclude that concomitant antacid or cimetidine does not alter the oral absorption or pharmacokinetic disposition of single-dose SCH 39304.  相似文献   
10.
We studied the mechanism of gastric emptying of a pH-sensitive radiotelemetry capsule with respect to phases of the interdigestive migrating motor complex (IMMC) in fasting normal volunteers and the effect of the Heidelberg capsule (HC) on the duration or timing of the IMMC phases. A manometric catheter with eight mounted solid-state strain gauges was passed transnasally and positioned fluoroscopically in the duodenum and jejunum in four normal, fasted male volunteers, in their right lateral position. The HC was administered orally following the establishment of one complete IMMC cycle (defined by the recording time between the end of two subsequent phase III activity fronts) and during the beginning of Phase I of the next cycle. The gastric residence time (GRT) of the HC was measured as the time of a gastric pH rise of 3.0 units. In three subjects, GRT of the HC lasted to within 5 min of the onset of the next duodenal phase III of the IMMC, while in the fourth subject, the HC passed during the second phase III activity front. There were no significant differences in the duration of each phase of duodenal IMMC in the presence or absence of the HC (Phase I, 54 ± 9.3 vs 31.6 ± 10.1; Phase II, 22 ± 8.1 vs 58.9 ± 32; Phase III, 5.3 ± 0.7 vs 4.2 ± 0.7 min; mean ± SE; P > 0.1 in all phases). In addition, the HC had no effect on motility index or patterns of contractions. The Heidelberg radiotelemetry device (7 × 20 mm) may be used as a noninvasive, nonradioactive means of measuring the activity of the IMMC and the presence of Phase III peak IMMC activity. Further, it permits detailed evaluation of the emptying patterns of solid dosage forms (i.e., enteric-coated tablet or controlled-release matrix) in humans under fasted or fed conditions.  相似文献   
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