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Biomedical subjects

D H Staniforth

Publications and source records attributed to D H Staniforth.

12 recordsLinked to original sources

Human pharmacology of renzapride: a new gastrokinetic benzamide without dopamine antagonist properties.

The activity of the substituted benzamide renzapride on the upper gastrointestinal tract has been investigated. It has been shown to enhance stomach emptying in normal subjects; doses of 2 and 5 mg decreasing by 21 and 37% respectively the volume of gastric contents aspirated 80 min after a test meal. Renzapride was found to reduce the oro-caecal transit time as assessed by the lactulose/breath hydrogen method in a dose related manner from 0.2 to 5 mg; the later dose producing a 62% reduction. Finally renzapride was shown not to elevate plasma prolactin at a dose of 5 mg, a finding consistent with lack of dopamine receptor antagonism.

Adult

Temocillin: lymph penetration and protein binding.

Temocillin, a novel betalactam antibiotic, was administered in doses of 1,2 and 4 g i.v. to 12 healthy subjects and the plasma concentrations of free and protein bound temocillin assayed and protein binding parameters were calculated. In a second study 2 g of temocillin was administered i.v. to 12 healthy subjects and samples of lymph were collected and assayed for total temocillin. Using the protein binding parameters so obtained the corresponding free temocillin in lymph was calculated. The clinical significance of the lymph penetration is discussed.

Adult

Statistical analysis of the lactulose/breath hydrogen test in the measurement of orocaecal transit: its variability and predictive value in assessing drug action.

The variability in the orocaecal transit time as measured by the lactulose/breath hydrogen method has been studied for three conditions: lactulose given with a meal, subjects sitting; lactulose given with a meal, subjects semirecumbent; lactulose given in aqueous solution, subjects semirecumbent. Thirty three healthy subjects attended on up to 12 occasions. It was found that administration of the lactulose with a meal significantly reduced the variability (p less than 0.05) and that adoption of the semirecumbent position further reduced variability. A power analysis was used to predict the number of subjects who would be required to show a given percentage change in orocaecal transit time at specified probabilities and powers. A graph and a table for use in the prediction of subject numbers at a probability of 5% and for powers of 50-99% is presented. A dose response curve for metoclopramide using the lactulose/breath hydrogen method is given for doses of 10, 15, and 20 mg.

Breath Tests

Comparison of orocaecal transit times assessed by the lactulose/breath hydrogen and the sulphasalazine/sulphapyridine methods.

The lactulose/breath hydrogen and the sulphasalazine/sulphapyridine methods of assessing orocaecal transit time have been compared. In a two part crossover study in healthy normal subjects the median orocaecal transit time by the SLZ/SP method was 4.84 hours but only 2.92 hours by the lactulose/breath hydrogen method. Coadministration of lactulose and sulphazalazine to nine subjects with assessment of orocaecal transit time by hydrogen breath determination and plasma sulphapyridine assay gave orocaecal transit times of 2.33 and 2.25 hours respectively suggesting that the lactulose reduces transit time and that the lactulose/breath hydrogen method, which is so convenient to use, gives artificially low transit times. A third experiment was undertaken to compare the orocaecal transit times after 1.5 and 3.0 g sulphazalazine. The orocaecal transit times after the two doses were not statistically different.

Adult

The variability in oro-cecal transit time assessed using a bean-based test meal and its use in the study of the effect of metoclopramide and BRL 24924 on transit time.

The inter and intra subject variation in the oro-cecal transit time assessed using the bean/breath hydrogen method was studied and analyzed to allow estimation of the number of patients/subjects required to show a drug-induced difference for given levels of statistical significance and power. Thus at the conventional 5% level of significance and for a test with 90% power, a dozen subjects should be sufficient to show a drug-induced change which is 25% or greater. Two crossover studies are described using 20 mg metoclopramide and 2 mg BRL 24924, orally, against placebo to investigate their action on oro-cecal transit time. Metoclopramide, 20 mg, produced a 45% reduction in the transit time compared with placebo. BRL 24924, 2 mg, in a similar study showed a 71% reduction.

Adult

Effect of drugs on oro-caecal transit time assessed by the lactulose/breath hydrogen method.

The comparative actions of two benzamides; the one metoclopramide, having and the other, BRL 20627, lacking dopamine receptor antagonist properties have been investigated on orocaecal transit time (OCTT) using the lactulose/breath hydrogen method. In addition, the action of codeine, propantheline and domperidone on OCTT has been assessed. Similar quantitative reductions in apparent OCTT were found with metoclopramide and BRL 20627 thus, metoclopramide 20 mg orally and 10 mg i.v. brought about 32.5% and 42% reductions in OCTT. Similar reductions were also found using 20 mg BRL 20627 orally and 10 mg i.v. (31 and 26% respectively). In addition 20 mg domperidone orally was found to cause a 10% reduction. Codeine orally and propantheline i.m. brought about increases in the assessed transit time.

Adult

An HPLC assay for sulphapyridine in plasma and its use to assess small bowel transit time after the administration of sulphasalazine.

An HPLC assay for sulphapyridine is described. The use of the assay to measure sulphapyridine produced by the action of large bowel flora on 2 g of orally administered sulphasalazine as a means of assessing oro-colonic transit time is discussed. The assay is applied to show the action on oro-colonic transit time of a novel gastrokinetic agent BRL 24924 which brought about a 62.8% median reduction in transit time at a dose of 5 mg.

Adult

Pharmacokinetics of parenteral ticarcillin formulated with clavulanic acid: Timentin.

The pharmacokinetics of a formulation of clavulanate potentiated ticarcillin (Timentin) have been investigated following a bolus intravenous injection of 1.2 g, infusions of 3.2 g over periods ranging from 30 minutes to three hours, and a bolus dose of 1.2 g followed by an infusion of 3.2 g. The effect of probenecid has also been investigated. The serum levels of clavulanic acid are discussed in relation to the microbiology and therapeutic implications.

Bacteria

Augmentin bioavailability following cimetidine, aluminum hydroxide and milk.

Previous studies [Jackson et al. 1980] have shown that the bioavailability of Augmentin is not affected by food. The present work has shown that aluminum hydroxide, milk and cimetidine do have some influence on the bioavailability of a single dose of oral Augmentin, but the small differences observed are unlikely to be of therapeutic importance. It is concluded that Augmentin may be administered in clinical practice with any of these substances.

Administration, Oral

The effects of dietary fibre on upper and lower gastro-intestinal transit times and faecal bulking.

A total of 10 obese patients (body mass index greater than 25) undergoing treatment with a very low-calorie (330 kcal/day) liquid diet were treated without and with 10.5 or 21 g/day dietary fibre. Mean (+/- SE) faecal bulking increased significantly (P less than 0.001) in a dose-dependent manner from 314.8 +/- 54.4 g on a fibre-free diet to 517.2 +/- 45.4 g and 748.9 +/- 78.5 g, respectively, over 5 days on diets containing 10.5 and 21 g/day dietary fibre. Total mean colonic transit time decreased from 53.9 +/- 3.6 h on a fibre-free diet to 25.8 +/- 44 and 17.3 +/- 4.6 h, respectively, on diets including 10.5 and 21 g/day dietary fibre. Both right and left colonic transit times were similarly affected but no effect on orocaecal transit time was detected.

Body Mass Index