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Biomedical subjects

D H Staniforth

Publications and source records attributed to D H Staniforth.

At least 19 recordsLinked to original sources
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1984

Parenteral augmentin: pharmacokinetics.

The pharmacokinetics of intravenous Augmentin have been investigated and the data found to fit a two compartment model. In the first study, to a crossover design, a bolus injection of 1.2 g Augmentin was given to 8 healthy volunteers with and without probenecid. It was found that the serum concentrations of amoxycillin were increased in the presence of probenecid, but those of clavulanic acid were unaffected. In a second study a further 8 volunteers received an infusion over 30 min of 2.2 g Augmentin. At the end of the infusion, peak concentrations in excess of 100 micrograms/ml were recorded for amoxycillin and 14 micrograms/ml for clavulanic acid. In both studies the serum and urinary concentrations of amoxycillin and clavulanic acid obtained were well above those considered necessary to achieve a therapeutic effect.

Adult↗
PubMed1983

Streptokinase and anisoylated streptokinase plasminogen complex. Their action on haemostasis in human volunteers.

A new fibrinolytic agent, BRL 26921, a member of the novel class of thrombolytic agents; the acyl enzymes, has been compared with streptokinase. It has been shown that this new agent, which can bind to fibrin before releasing activator, does not result in clinically significant destruction of the haemostatic system when compared to an equivalent dose of streptokinase.

Adult↗
PubMed1983

Systolic time intervals: the effect of stroke volume in healthy young men.

1. Positional change and exercise were used to gain a range of heart rates and stroke volumes in 20 healthy male subjects, and a regression plane computed for the 3 principal systolic time intervals. The addition of stroke volume as a second physiological variable was shown to result in an increase in the coefficient of determination of 13% for the LVET and 10% for the PEP. The QS2 was found to be dependent only on heart rate. It is concluded from this preliminary study that the addition of stroke volume and the derivation of a planar regression equation would allow calculation of potentially more useful index values for the LVET and PEP.

Adult↗
PubMed1983

Amoxycillin/clavulanic acid: the effect of probenecid.

The effect of probenecid on the combination of amoxycillin/clavulanic acid has been compared with the effect on amoxycillin alone and it has been shown that probenecid, whilst producing its expected effect on amoxycillin, did not affect the clavulanic acid concentration of the combination. A possible minor role for tubular secretion of clavulanic acid is discussed.

Adult↗
PubMed1983

The QT interval and cycle length: the influence of atropine, hyoscine and exercise.

Twenty-seven healthy male subjects of mean age 24.3 +/- 4.0 years and mean weight 74.9 +/- 9.1 kg took part in an investigation to assess the most suitable correction for the QT interval as a function of cardiac cycle length. 547 sets of data points were generated. Atropine 0.6, 1.2 and 1.8 mg, and hyoscine 0.4 and 0.8 mg, and exercise on a bicycle ergometer at power levels of 50-250 watts together with post-exercise values were employed to obtain a range of heart rates. Simultaneous measurement of cardiac output and total peripheral resistance were made. It was found that the traditional square root formula gave an unsatisfactory correction for the QT for supine subjects following atropine and hyoscine. The formula K = QT/RRN was linearized and fitted to the data by the least squares method and gave a best fit correction with N = 0.35, which is close to the cube root correction of Fridericia (1920). Neither stroke volume nor total peripheral resistance were found to provide a further enhancement of the correction. The relationship between QT and cycle length following the exercise protocol was found to be best represented by Bazett's correction but the complex changes in the QT produced by exercise were noted. These findings support the suggestion that either the cube root correction or the best fit correction with N = 0.35 provides a better correction factor than the traditional square root correction for the QT interval in clinical pharmacology experiments for data generated in resting patients.

Adult↗
PubMed1980

Propranolol and blood glucose: simultaneous measurements over a wide range of doses and the effect of propranolol on the glucose tolerance test.

No correlation was found between blood glucose and simultaneous measurements of plasma propranolol concentration in patients with schizophrenia, on a daily dose of 80 mg to 1800 mg of propranolol as an adjunct to phenothiazine medication. The Glucose Tolerance Test (GTT) in ten patients on propranolol and phenothiazines did not differ significantly from those of a matched control group on phenothiazine alone. Two patients with mild diabetes showed no significant change in their GTT after stopping propranolol. These observations accord with the view that relatively high doses of propranolol as an adjunct to phenothiazine medication in schizophrenia are safe from the standpoint of glucose metabolism. This does not apply to the insulin dependent diabetic who is in danger of severe hypoglycaemia when glycogenolysis is blocked by propranolol.

Adipose Tissue↗