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Biomedical subjects

W L Burland

Publications and source records attributed to W L Burland.

At least 19 recordsLinked to original sources
PubMed1987

Large single daily dose of histamine H2 receptor antagonist for duodenal ulcer. How much and when? A clinical pharmacological study.

The effects of single doses of cimetidine 800, 1200, and 1600 mg, given at 2300 h or 800, and 1600 mg at 1800 h, have been studied in patients with duodenal ulcer disease in symptomatic remission, and compared with cimetidine 400 mg bd (0800 h and 2300 h) and ranitidine 300 mg (given at 1800 h) respectively. A dose related reduction in intragastric acidity was seen. All single nocturnal (2300 h) doses of cimetidine produced anacidity overnight. This was not achieved with dosing at 1800 h although the duration of inhibition of gastric acidity was longer. Inhibition of overnight acid and pepsin outputs were similarly dose and timing related, but inhibition of peptic activity was much less after dosing at 1800 h. Cimetidine 1600 mg and ranitidine 300 mg were similar in their effects.

Adult↗
PubMed1985

Cardiovascular responses in healthy subjects to a novel oral dopamine agonist, fenoldopam.

Two double-blind randomized crossover studies were carried out in healthy male subjects to determine the cardiovascular effects of fenoldopam and to assess whether they could be modified by metoclopramide. Blood pressure (BP) and heart rate (HR) were measured supine and upright, before and for up to 4 h after dosing. Single oral doses of fenoldopam 50, 100 or 150 mg or placebo were administered in one study. In the other study, subjects received 20 mg metoclopramide or placebo intravenously, 20 min before an oral dose of 100 mg fenoldopam or placebo. Fenoldopam produced decreases in diastolic BP and increases in HR indicative of an orally active systemic arteriolar vasodilator. Mean peak responses occurred 30-60 min after dosing and values had returned to pretreatment levels within 3-4 h. The decrease in diastolic BP was partially attenuated by pretreatment with metoclopramide. Thus, at least in part, the fall in BP following fenoldopam could be due to an interaction with dopamine receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1984

The pharmacokinetics in man of SK&F 93319--a new antagonist of histamine H1 and H2 receptors.

SK&F 93319, a potent histamine H1- and H2-receptor antagonist, is rapidly absorbed with a low rate of plasma clearance primarily by metabolism. Excretion is divided evenly between urine and faeces (probable biliary elimination) with little unchanged drug in the urine. Serum protein binding at low concentrations is very extensive and appears to restrict distribution of SK&F 93319. At higher concentrations (higher dose levels) reduced protein binding results in a marked proportional increase in available free drug with a consequent increase in distribution and clearance. Bioavailability is reduced at higher dose levels. The importance of factors contributing to non-linear pharmacokinetics and the potential clinical consequences are demonstrated.

Adult↗
PubMed1982

Oxmetidine: clinical pharmacological studies with a new H2-receptor antagonist.

The gastric antisecretory effects of oxmetidine, a new H2-receptor antagonist, have been studied in 33 healthy subjects. The relative potency of oxmetidine compared with that of cimetidine depended on the route of administration and the experimental conditions. Oxmetidine intravenously infused was approximately four times as potent as cimetidine, weight for weight, in inhibiting impromidine stimulated gastric acid secretion but was twice as potent when food was used as a stimulus. After oral administration there were no differences in the weight-for-weight potency of oxmetidine and cimetidine, although oxmetidine was twice as potent on a molar basis. These apparent differences according to the route of drug administration are probably due to first pass metabolism of oxmetidine. There were no differences in the duration of action of oxmetidine and cimetidine. Twenty-four hour monitoring of intragastric pH showed that oxmetidine 400 mg twice daily reduced mean hourly 24 hour intragastric pH by 59%, suggesting that a twice daily dosage regimen should be evaluated in the treatment of duodenal ulceration.

Adolescent↗
PubMed1981

Cardiovascular effects in man of intravenous prizidilol hydrochloride (SK&F 92657); a new antihypertensive agent.

1 Cardiovascular responses to intravenous prizidilol hydrochloride (SK&F 92657) 0.86 mg/kg were studied in eight supine resting healthy volunteers. Five subjects were slow and the remaining three were fast acetylators of sulphamethazine. Compared with pre-infusion values, mean resting systolic and diastolic blood pressures were significantly reduced, while mean resting pulse rate was significantly increased at 30 min after the start of the twenty minute infusion. 2 During the 6 h study period the lowest mean +/- s.e. mean systolic blood pressure (108.8 +/- 1.7) was recorded 30 min after the start of the infusion. This represented a mean reduction of 5.2 mmHg. Reductions in mean diastolic blood pressure were greater and of longer duration, the lowest mean value (44.8 +/- 2.0 mmHg) being recorded 3.5 h after the start of the infusion and representing a reduction of 18.5 mmHg from the pre-dosing value. At 6 h after the start of the infusion mean diastolic blood pressure was still significantly reduced (by 15.3 mmHg). 3 The maximum mean +/- s.e. mean resting pulse rate (79.3 +/- 4.4 beats/min) occurred 3 h after the start of the infusion, an increase of 23.0 beats/min over the pre-infusion value. At the end of the study the pulse rate was still significantly raised (by 17.7 beats/min). 4 The left ventricular ejection fraction, evaluated in five subjects, 45 min after the start of the infusion, was not altered by prizidilol hydrochloride, but the left ventricular area decreased significantly. 5 Intravenous prizidilol hydrochloride decreases resting blood pressure and left ventricular area, increases pulse rate and has virtually no effect on left ventricular ejection fraction.

Adolescent↗
PubMed1980

Cimetidine treatment for the prevention of recurrence of duodenal ulcer: an international collaborative study.

Comparison of cimetidine and placebo in the prevention of recurrence of ulceration was carried out in the study of 696 patients with recently healed duodenal ulcers. Treatment with cimetidine 400 mg at bedtime or twice daily for up to 12 months very significantly reduced recurrence of symptomatic ulceration. Asymtomatic ulceration occurred in treated and untreated patients but was found significantly less often in cimetidine-treated patients. There were no serious untoward effects of cimetidine treatment. Only 3 patients (0.8%) were withdrawn for possible drug-related reasons. Evidence from other studies suggests that the natural history of duodenal ulcer remains unaltered when cimetidine treatment is stopped after one year. Investigations have been planned to study the efficacy and safety of longer periods of treatment.

Adolescent↗
PubMed1980

Prolactin responses to histamine H2 receptor antagonists.

We have compared the effects of cimetidine and SK&F 92994, a new more potent histamine H2 receptor antagonist, on serum prolactin, and also assessed the effect of the H2 receptor agonist impromidine on the response to cimetidine. As previously reported, cimetidine 200 mg given as an iv bolus dose produced a marked rise in serum prolactin, but 50 mg and 200 mg of SK&F 92994 given by the same route had no effect. Iv infusion of impromidine 10 microgram kg-1h-1 failed to modify the prolactin response to cimetidine. It is concluded that the rise in serum prolactin following iv administration of cimetidine may be due to a specific property of cimetidine. An effect mediated via histaminergic pathways within the central nervous system, although less likely, cannot be excluded.

Cimetidine↗
PubMed1980

Gastric secretory studies in humans with impromidine (SK&F 92676)--a specific histamine H2 receptor agonist.

Impromidine (SK&F 92676), a potent selective histamine H2-receptor agonist in animals has been studied in healthy male volunteers. Impromidine 10 micrograms kg-1h-1 i.v. produced near maximal acid secretion and cimetidine 2 mg kg-1h-1 inhibited this output by a mean of 65% in 5 subjects. The log dose-response curve to impromidine in 5 subjects was linear over the dose range 2.5--20 micrograms kg-1h-1. Cimetidine 0.5 mg kg-1h-1 caused a highly significant parallel shift of the dose-response curve, consistent with direct competitive antagonism. The gastric secretory responses to impromidine 10 micrograms kg-1h-1 i.v., histamine acid phosphate 40 micrograms kg-1h-1 i.v., and pentagastrin 6 micrograms kg-1h-1 i.v. were similar. Cardiovascular effects of impromidine were less marked than those due to histamine. Gastric secretory and cardiovascular effects of impromidine are dose dependent. No significant difference was seen in peak acid output between impromidine 10 micrograms kg-1 and pentagastrin 6 micrograms kg-1 whether injected intramuscularly or subcutaneously. Headache which accompanied infusion with histamine occurred less frequently with impromidine, and nausea and abdominal discomfort which occurred with pentagastrin did not occur with impromidine. Impromidine will be valuable in the study of gastric secretion and the role of histamine H2 receptors in other systems.

Adolescent↗
PubMed1979

Prolactin responses to cimetidine.

1 An intravenous injection of cimetidine 400 mg to four healthy male subjects resulted in high blood concentrations of cimetidine and a rapid three-fold increase in serum prolactin. 2 This effect was prevented by pretreatment with bromocriptine. 3 No increase in prolactin followed a single oral dose of cimetidine 800 mg administered to a different group of healthy male subjects. The mean peak blood concentration of cimetidine was less than 20% of that achieved with 400 mg i.v. 4 Only isolated reports have been received of gynaecomastia or galactorrhoea occurring during cimetidine treatment. In three of seven cases studied there was associated hyperprolactinaemia. This may be an idiosyncratic response at the lower blood concentration of cimetidine associated with oral therapeutic dose regimens.

Administration, Oral↗