Biomedical subjects

D W Burget

Publications and source records attributed to D W Burget.

At least 19 recordsLinked to original sources

PubMed1994

Appropriate acid suppression for optimal healing of duodenal ulcer and gastro-oesophageal reflux disease.

Comparisons of the effectiveness of treatments for healing duodenal ulcer are essential to determine optimal management strategies for both economic analysis and quality-of-life evaluation. Differences are usually made on the basis of the proportion of ulcers healed at varying time intervals. It has been shown by meta-analysis that healing of duodenal ulcers with antisecretory drugs is directly correlated to the degree of acid suppression. More recently, sophisticated meta-analysis of 24-hour intragastric acidity data and clinical trials of antisecretory drugs has demonstrated that the optimal degree and duration of gastric acid suppression for healing duodenal ulcer can be achieved by an aggregate time above pH 3 of 18-20 hours/day. These conditions predict 100% ulcer healing at 4 weeks. Antisecretory drug regimens that approach these criteria should achieve faster healing than other agents, with a concomitant acceleration of symptom resolution. Regression analysis was performed on the healing-time curves for each drug class to determine the rate of ulcer healing per week. The mean proportion of ulcers healed, irrespective of treatment duration, was highest for omeprazole, which also provided a significantly faster rate of duodenal ulcer healing than all other drug classes (p < 0.001). It has recently been shown that healing of erosive oesophagitis with antisecretory drugs is directly correlated with both the duration of acid suppression over the 24-hour period (p < 0.05) and the elevation of intra-oesophageal pH above 4. Furthermore, oesophageal acid exposure time can be normalized by maintaining the intra-oesophageal pH above 4 for at least 96% of the 24-hour period.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis↗

PubMed1992

Omeprazole (20 mg) daily given in the morning or evening: a comparison of effects on gastric acidity, and plasma gastrin and omeprazole concentration.

Although omeprazole has a long duration of action and has usually been given in the morning, there are theoretical advantages in administering antisecretory drugs in the evening as has been shown for the H2-receptor antagonists. The aim of this study was to compare the effects of placebo and 20 mg omeprazole given either in the morning or evening, on gastric acidity, plasma gastrin levels and plasma omeprazole in 6 duodenal ulcer patients. The 24-hour mean pH (+/- S.E.M.) was: placebo 1.7 +/- 0.1; morning doing, 3.9 +/- 1.8 (P less than 0.01); evening dosing, 2.9 +/- 1.1 (N.S.). There was a large inter-individual variability of intragastric acidity in response to omeprazole, which was reflected both in the plasma gastrin and in the area under the plasma omeprazole concentration-time curve. Morning administration of omeprazole is optimal, but variability in the patient response to 20 mg omeprazole is still seen.

Double-Blind Method↗

PubMed1990

Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression.

The optimal degree and duration of suppression of gastric acidity required for the healing of peptic ulcers has never been established. Although very potent inhibitors of acid secretion are now available, the need for this degree of suppression has not been shown, and there is a possibility of adverse effects because of pronounced acid inhibition. Therefore, a model has been constructed that defines the relationship between duodenal ulcer healing and antisecretory therapy. Acid suppression data were obtained directly from investigators as raw data from 24-hour studies of acid secretion. Twenty-one experiments from seven investigators provided 490 24-hour studies using 19 different treatment regimens. Healing data were collected from a metaanalysis of published clinical trials of duodenal ulcer healing. A total of 144 published trials in 14,208 patients provided healing data at several endoscopic endpoints for the 19 drug regimens for which acidity data were provided. Weighted least-squares polynomial regression analysis was used to define those parameters of antisecretory therapy that contributed most to duodenal ulcer healing and to define the shape of the response surface. A highly significant correlation (r = 0.9814) was found between healing and the degree of acid suppression, the duration of acid suppression, and the length of therapy. The shape of the contour expression this relationship shows that healing increases as the duration of suppression increases and as gastric pH increases. However, suppression that increased pH beyond 3.0 was not found to increase ulcer healing further. It is concluded that a longer duration of antisecretory effect and/or a longer duration of therapy are of greater importance than potency for duodenal ulcer healing.

Antacids↗

PubMed1990

Twenty-four-hour intragastric acidity and nocturnal gastric secretion in gastric ulcer patients--the effects of cimetidine.

In a double-blind randomized study, the profile of 24-h intragastric acidity and nocturnal gastric secretion was measured in a group of patients with healed gastric ulcer on placebo and 400 mg cimetidine b.d. and 800 mg nocte. Neither cimetidine regimen significantly decreased daytime intragastric acidity, but the 800 mg nocte dose caused a significant decrease in both nocturnal acidity (18.1 to 5.5 mmol/L; P less than 0.05) and acid output (11.0 to 1.7 mmol 7 h; P less than 0.05). The decrease in nocturnal gastric secretion by 400 mg cimetidine b.d. was not significant. As in duodenal ulcer, 800 mg cimetidine nocte will effectively suppress night-time acid secretion in patients with gastric ulcer while leaving acid secretion during the day unaffected.

Adult↗

PubMed1990

Do hourly averaged pH readings correlate with those from point readings of aspiration? Comparison of two different electrode positions with simultaneous aspiration.

Hourly averaged data from continuous intraluminal pH recording were compared with the point aspiration in five 24-hour studies performed on healthy volunteers. Two different electrode positions were compared simultaneously with aspiration. The correlation was performed using the median from the whole hour's recording of the electrode against the aspiration point. There was a significant correlation between both electrodes and aspiration (p less than 0.001), although both electrodes read consistently lower than aspiration: electrode A (gastric antrum), median pH = 1.4; electrode B (gastric body), pH = 1.9; aspiration, pH = 2.3. These findings show that data reported in clinical trials using different recording techniques are not directly comparable and must be interpreted appropriately. The position of the electrode may also be important.

Adult↗

PubMed1989

Does misoprostol given as a single large dose improve its antisecretory effect?

H2-receptor antagonists have been shown to be effective in the suppression of nocturnal acidity. This double-blind, randomized, crossover Latin-square study of 24-h intragastric pH in 12 normal volunteers investigated the effect of large single-dose administration of misoprostol on intragastric acidity. Efficacy of 800 micrograms misoprostol h.s., 600 micrograms h.s., 400 micrograms h.s. and 800 micrograms after supper was compared to placebo and 200 micrograms misoprostol q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. 2.2 +/- 0.3, 800 micrograms p.m. 2.6 +/- 1.1, 400 micrograms h.s. 2.6 +/- 0.7, 600 micrograms h.s. 2.6 +/- 0.4, 800 micrograms h.s. 2.6 +/- 0.5. The effect of misoprostol on gastric acidity was short and limited to the nocturnal period. Only misoprostol 800 micrograms and 600 micrograms reduced 24-h acidity compared to placebo (P less than 0.04).

Adult↗

PubMed1989

Do H2 receptor antagonists have to be given at night? A study of the antisecretory profile of SKF 94482, a new H2 receptor antagonist which has a profound effect on daytime acidity.

Evening dosing has become standard for H2 receptor antagonists, because available agents inhibit nocturnal basal acid secretion more effectively than daytime stimulated secretion. We studied the optimal time of administration of a new high affinity long acting H2 receptor antagonist, SKF 94482, for the suppression of intragastric acidity using intragastric telemetry. Sixteen healthy subjects received SKF 94482 200 mg or placebo at 07:30, 17:30, and 21:30 h during four separate studies. Time (h) above pH 4 was (mean (SD] 1.1 (1.2) on placebo, 7.8 (5.0) on SKF 94482 given at 07:30, 5.75 (3.6) on SKF 94482 given at 17:30, and 6.1 (2.9) when given at 21:30. All treatment regimens were effective in increasing time above pH 4 (p less than 0.01). The efficacy of the morning dose of SKF 94482 indicates that the best time to give H2 receptor antagonists depends on their pharmacological properties.

Adult↗

PubMed1989

Validation of pH dataloggers for pharmacologic studies.

Twenty-four-hour gastric aspiration studies have been superseded by dataloggers that continuously record intragastric pH. We have studied both techniques in a practical pharmacologic study, comparing early evening versus nighttime dosing with ranitidine and nizatidine against placebo. Whereas there was a highly significant point correlation between aspiration and datalogger pH, the slope was significantly less than 1. The correlation was poorer during the day (r = 0.51) than at night (r = 0.83). Irrespective of the techniques used, however, conclusions reached on drug efficacy were similar, but direct comparison of data from the two techniques is not possible.

Circadian Rhythm↗

PubMed1988

The treatment of gastric ulcer with antisecretory drugs. Relationship of pharmacological effect to healing rates.

Published clinical trials (N = 56) of antisecretory drugs in the treatment of benign gastric ulcer were reviewed. Composite healing rates for various drug regimens were calculated using a method previously described for duodenal ulcer. Healing rates were compared with data on suppression of intragastric acidity to see if any relationship was evident. No significant correlations between the two existed, unless placebo data were included in the analysis. Correlations were stronger with suppression of total 24-hr rather than nocturnal acidity. Using Williams' method for assessing trends, it was found that an increase in antisecretory effect is not associated with a concomitant increase in healing rates. Duration of medical treatment is the single most important factor in healing of benign gastric ulcer; healing rates for all drug regimens and placebo show a consistent increase with prolongation of treatment.

Anti-Ulcer Agents↗

PubMed1988

Alteration of H2 receptor sensitivity in duodenal ulcer patients after maintenance treatment with an H2 receptor antagonist.

The effects of a specific H2 receptor agonist impromidine, on gastric acid secretion were measured in six patients with duodenal ulcer in clinical remission before and after three months treatment with ranitidine 150 mg nocte. After treatment basal acid output increased from 1.2 to 2.8 mmol/h and after maximal impromidine stimulation from 36.9 (4.7) to 44.2 (6.2) mmol/h (p less than 0.02). Intravenous ranitidine 50 mg was given at the end of the impromidine infusion on each study day; the antisecretory effect of intravenous ranitidine was accentuated after the treatment with ranitidine from a trough acid output of 8.5 (1.2) mmol/h before, to 3.8 (1.5) mmol/h (p less than 0.05) after, treatment. The increased response to the H2 agonist impromidine and the H2 antagonist ranitidine after treatment with ranitidine suggests an enhanced sensitivity of the H2 receptor. This might be explained on the basis of an increase in the number of H2 receptors ('up-regulation').

Adult↗

PubMed1987

The effects of intravenous famotidine on pentagastrin-stimulated gastric secretion in man.

Eight healthy male volunteers were each studied on four occasions in a 7 hour double-blind, placebo-controlled experiment. Three continuous 6 hour intravenous (i.v.) infusion rates of famotidine, calculated to achieve steady-state plasma concentrations of 10, 30 and 90 ng ml-1, were compared to placebo. Commencing at the third study hour, hourly incremental step-up i.v. infusions of pentagastrin 0.1, 0.2, 0.5, 1.0 and 2.0 micrograms kg-1. hour were administered on each of the four study days. Hourly blood samples were taken for the subsequent determination of plasma famotidine concentration. The three famotidine infusion rates inhibited basal gastric secretion. Pentagastrin-stimulated secretion was inhibited in a dose-dependent manner. The highest dose of famotidine (38.7 micrograms kg-1.hour) inhibited each infusion rate of pentagastrin-stimulated gastric secretion between 92 and 96%. The lowest dose of famotidine (4.3 micrograms kg-1.hour) inhibited pentagastrin 0.1 micrograms kg-1.hour stimulated secretion by 50% but, when stimulated with pentagastrin 2.0 micrograms kg-1.hour, gastric secretion was inhibited by only 25%. This study indicates that the intravenous preparation of famotidine is a potent inhibitor of pentagastrin-stimulated gastric acid secretion.

Adult↗

PubMed1987

Marked suppression of stimulated gastric acid and pepsin secretion by enisoprost, a new PGE1 analogue.

The gastric antisecretory effects of three different doses of enisoprost, a new synthetic PGE1 analogue, were compared with placebo and misoprostol in 20 healthy male volunteers. Enisoprost 100, 200 and 400 micrograms all significantly (P less than 0.0001; ANOVA) suppressed histamine-stimulated acid and pepsin output when compared with placebo or misoprostol 200 micrograms. Misoprostol produced a significant decrease of stimulated acid output when compared with placebo (P = 0.0012). The concentration of pepsin in gastric juice was significantly (P less than 0.0001) decreased by enisoprost at the commencement of histamine stimulation. This effect was short-lived, and was maximal with enisoprost 400 micrograms. There was a significant dose-response relationship for enisoprost for inhibition of stimulated acid output (P = 0.0065). Enisoprost was well tolerated, and no consistent drug-related adverse effects were detected. The profile of antisecretory effect of enisoprost, producing marked suppression of both acid and pepsin secretion independently, is unusual. This combination of activity along with any mucosal protective properties might be particularly effective in the treatment of peptic ulcer disease.

Adult↗

PubMed1987

Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs.

FVMany different dosage schedules of antisecretory drugs for the treatment of duodenal ulcer are recommended. The relationship between degree of acid suppression and therapeutic efficacy has not been precisely defined for these drugs. We have examined the association between suppression of intragastric acidity and duodenal ulcer healing rates for a number of therapeutic regimens. For the H2 receptor antagonists alone, the most significant correlation with healing rates was with suppression of intragastric acidity at night (r = 0.926; p = 0.0001). When other classes of drug: high dose antacid, omeprazole and a synthetic prostaglandin (enprostil) were included in the analysis, the closest correlation was with suppression of total 24 hour intragastric acidity (r = 0.911; p less than F0.0001). Stepwise linear regression analysis was used to investigate the relative contributions to healing of suppression of acidity during the day and night. Suppression of nocturnal acidity was found to be the single most important factor in explaining healing rates. No further benefit was obtained with daytime suppression for H2 receptor antagonists; suppression of acidity at night accounted for 86.1% of the observed variation in healing rates among different regimens of H2 receptor antagonists. When all classes of drugs were analysed, inclusion of daytime suppression produced a significant improvement in correlation over nocturnal suppression alone. Drug regimens providing potent suppression of nocturnal acidity produce the highest healing rates in controlled clinical trials. The healing rate for any dose regimen of an antisecretory drug can be predicted from a knowledge of its effect on intragastric acidity. For the H2 receptor antagonists, suppression of nocturnal acidity is the most relevant in this context. Moderate suppression of acidity achieves ulcer healing rates at four to eight weeks which are comparable with those seen with potent suppression at two to four weeks. Increasing degrees of suppression merely accelerate healing.

Anti-Ulcer Agents↗

PubMed1987

A double-blind randomized study comparing different dose regimens of H2-receptor antagonists on 24-hour gastric secretion in normal subjects and duodenal ulcer patients.

Duodenal ulcer therapy with H2 antagonists initially aimed to control acid secretion throughout the 24-h period, but recently nighttime suppression has been advocated. The effect of single nighttime regimens of cimetidine 400 mg BID, cimetidine 800 mg HS, ranitidine 150 mg HS, and placebo on 24-h intragastric acidity, nocturnal acid output, and pepsin secretion were studied in four healthy volunteers and four patients with healed duodenal ulcer. A nonrandomized dose of cimetidine 1200 mg HS was also studied. For all four treatments, daytime (0730-2230 h) intragastric acidity was reduced by 4-30% in the normals and by 10-44% in the duodenal ulcer patients (NS), while 24-h intragastric acidity was reduced by 44-46% and 40-64%, respectively (p less than 0.05). Reduction in nocturnal acid output was 82-96% in normals and 91-99% in duodenal ulcer, respectively. Pepsin concentration was unaffected by treatment but pepsin concentration was significantly (p less than 0.05) lower in patients than in normals. Mean 24-h gastric acid secretion was reduced by a single nighttime treatment with an H2-receptor antagonist, while nocturnal acid secretion was virtually abolished. H2 antagonists given only at night deserve further clinical evaluation to determine the minimal effective dose and optimal duration of suppression to achieve ulcer healing.

Cimetidine↗

PubMed1986

Comparison of the effects of gastric antisecretory agents in healthy volunteers and patients with duodenal ulcer.

Thirty published studies of the clinical pharmacology of gastric antisecretory agents in normal volunteers and duodenal ulcer patients were reviewed. The aim was to investigate the relationship between antisecretory effect in the two populations. There was a significant correlation between effect in patients and normal subjects for suppression of 24 hour intragastric acidity (r = 0.732; p = 0.0068), nocturnal intragastric acidity (r = 0.861; p = 0.0033) and nocturnal acid output (r = 0.964; p = 0.0069). The regression lines for 24 hour and nocturnal acidity were very similar. The expected antisecretory effect of a particular dosage regimen in patients with duodenal ulcer can be predicted mathematically from data derived from studies in normal volunteers.

Anti-Ulcer Agents↗

PubMed1986

The effect of temperature and pH on the stability of human pepsin in stored gastric juice. A method to prevent activity loss.

The mechanisms controlling pepsin secretion are controversial. A contributory factor may be storage-dependent effects. We have studied the effects of temperature, pH, and storage time on human gastric pepsin. Gastric juice samples taken from three healthy volunteers under both basal and post-pentagastrin-stimulated (6 micrograms/kg subcutaneously) conditions were separated into four aliquots. Each aliquot was titrated to pH 1, 4, or 6 or left at ambient pH. Aliquots were then stored at 4 degrees C or frozen at -70 degrees C and stored. On days 1, 3, 7, and 28 aliquots were removed and assayed by the kinetic albumin-bromphenol blue method. In a second experiment we determined the effects of different concentrations of glycerol on the preservation of peptic activity. From these experiments we conclude that pepsin is unstable when stored frozen at low pH but not when stored above pH 2. This pH-dependent stability may explain the variable conclusions other workers report on optimal methods of storing gastric juice. In addition, we have confirmed the suitability of glycerol as a preservative of peptic activity and recommend that gastric juice be stored frozen with 11.5% glycerol.

Cold Temperature↗

PubMed1986

The correlation between acid suppression and peptic ulcer healing.

Suppression of gastric acid forms the basis of treatment of duodenal and gastric ulcer, but the precise relationship between suppression of acidity and healing rates has not been defined. We examined the results of controlled trials and clinical pharmacological studies of 24-h intragastric acidity involving antisecretory agents. Data on 24-h and nocturnal hydrogen ion activity and nocturnal acid output were obtained, and the healing rates in duodenal ulcer were calculated. Duodenal ulcer healing rates after 4 weeks showed a significant correlation with suppression of 24-hour hydrogen ion activity (r = 0.63; P less than 0.05), and a highly significant correlation between healing and the suppression of nocturnal hydrogen ion activity (r = 0.93; P less than 0.0001). Nocturnal acid output was not significantly correlated. For gastric ulcer, no such association was seen for suppression of either 24-hour or nocturnal hydrogen ion activity. Duodenal ulcer is regarded as an acid-related disorder, but in gastric ulcer other factors may be more important in pathogenesis and treatment.

Anti-Ulcer Agents↗

PubMed1986

Effects of low dose omeprazole on gastric secretion and plasma gastrin in patients with healed duodenal ulcer.

The effects of seven days' treatment with omeprazole 5 and 10 mg daily on 24 hours gastric secretion and plasma gastrin concentrations were studied in a randomised double-blinded placebo-controlled study of six male patients with healed duodenal ulcer. Omeprazole 5 mg daily reduced mean daytime and nocturnal intragastric acidity by 31.4 and 40.1%, respectively. Omeprazole 10 mg per day produced very similar reductions of 33.6 and 42.0%, respectively. Total nocturnal acid output was reduced by 63.9% and 63.2%, respectively, by omeprazole 5 and 10 mg daily. There was a large degree of inter-subject variability in response to these low doses of omeprazole. Consequently, neither dose showed a statistically significant antisecretory effect when compared with placebo. Neither dose of omeprazole significantly affected fasting levels of gastrin, but omeprazole 10 mg daily produced a significant (P less than 0.05) increase in the integrated gastrin response to a meal. The lack of consistent antisecretory effect to low dose omeprazole is in accord with previous studies. This suggests that doses of 20 mg per day or greater are required to produce a consistent effect on acid secretion.

Adult↗