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Biomedical subjects

M Aylward

Publications and source records attributed to M Aylward.

At least 19 recordsLinked to original sources
PubMed1984

[Treatment of morning migraine. Clinical and biokinetic correlation of programmed-release dihydroergotamine].

The authors have tested a new preparation of dihydroergotamine (microgranules in a capsule) by comparing the clinical results obtained in 30 patients suffering from morning migraine with the plasma levels of the active substance measured in 8 healthy subjects. The microgranules were administered in doses of 30 mg/24 hours and compared with a similar dose of a dihydroergotamine solution. The close correlation observed between sustained plasma levels and prolonged therapeutic effects indicates a truly programmed delivery of dihydroergotamine by the microgranule preparation.

Adolescent↗
PubMed1984

Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects.

Plasma kinetics of dextromethorphan (as dextrorphan ) and codeine were investigated after acute oral doses in 8 patients with pathological cough; after which the patients participated in an acute dose-response study of the antitussive effects of each drug administered as syrups. Maximum plasma codeine concentrations averaged 384 ng.ml-1 (s.d. +/- 78.3) occurring between 0.75 and 2h after ingestion of 60 mg codeine phosphate; in comparison mean peak plasma dextrorphan levels were 386 ng.ml-1 (s.d. +/- 107.2) and 388 ng.ml-1 (s.d. +/- 101.3) respectively, after administration of 60 mg dextromethorphan syrup and tablet formulations. Bioavailability of dextromethorphan tablets was comparable to syrup. No correlation emerged between instantaneous plasma concentrations of either dextrorphan or codeine and antitussive responses; however, peak antitussive effect was significantly related to log dose with both drugs. Antitussive effects of 30 mg codeine phosphate and 60 mg dextromethorphan hydrobromide did not differ significantly; both were superior to 30 mg dextromethorphan hydrobromide and placebo.

Administration, Oral↗
PubMed1983

On the treatment of migraine. Pharmacokinetic-pharmacodynamic relationships for a programmed release formulation of dihydroergotamine administered orally in the human.

With the combined pharmacokinetic-pharmacodynamic approach, the bioavailability and venoconstrictor effects of two DHE formulations (programmed release capsules and oral solution) have been compared after acute oral dose administrations in the healthy volunteer subjects. The bioavailability of DHE from programmed release capsules has been significantly greater than that shown by the oral solution. DHE capsules formulation has seemed to provide appropriate plasma concentrations for at least 10 h after administration. That may well account for its efficacy in the treatment of morning migraine.

Administration, Oral↗
PubMed1983

Pharmacokinetics of 14C CDP-choline.

The absorption, metabolism and excretion of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) were investigated in six adult healthy subjects after a single oral dose of 300 mg of the 14C-labelled compound. The compound was well tolerated by the subjects. Absorption was virtually complete with less than 1% of the dose being found in the faeces during the 5-day collection period. Two peaks were found in the plasma radioactivity time profile: the first at 1 h, and a second larger peak at 24 h post-dose. Elimination of the ingested dose occurred via respiratory CO2 and through urinary excretion; the former predominating, and both routes exhibited biphasic patterns characterized by an early phase followed by slower decline. It is postulated that in the healthy human subject CDP-choline is metabolized in the gut wall and in the liver; the products arising from the compound's extensive hepatic metabolism being subsequently available for diverse biosynthetic pathways, tissue metabolism, and excretion.

Adult↗
PubMed1982

Long-term monitoring of the effects of thymoxamine hydrochloride tablets in the management of patients with Raynaud's disease.

Seventeen patients with Raynaud's disease were followed whilst receiving treatment with 40 mg thymoxamine hydrochloride 4-times daily for period ranging between 11 and 19 months. Digital artery patency and blood flow changes, assessed by Doppler ultrasound techniques after different thermal stresses, were monitored regularly as were platelet aggregation to ADP and collagen, platelet adhesion to glass beads, measures of blood coagulation and fibrinolysis, and plasma viscosity. Significant clinical improvement noted at 1 month appeared to improve further at 3 months and was maintained thereafter. Vessel patency rates at 10 degrees C and 21 degrees C improved significantly during treatment and both collagen- induced aggregation and platelet retention were significantly inhibited. These unexpected effects on platelet function are not readily explained by the drug's documented activity as a selective alpha-adrenergic antagonist and they may represent other hitherto unrecognized pharmacological effects which merit further exploration. The study also confirmed the usefulness of Doppler techniques for continuous atraumatic evaluation of digital vessel patency and investigation of therapeutic regimens on intermittent digital artery obstruction in Raynaud's disease.

Adult↗
PubMed1978

Clinical therapeutic evaluation of methylcysteine hydrochloride in patients with chronic obstructive bronchitis: a balanced double-blind trial with placebo control.

A double-blind, between-patient, placebo controlled trial was carried out to investigate the effects of methylcysteine hydrochloride in patients with chronic obstructive bronchitis. After a 2-week washout period on placebo, 30 patients were allocated at random to treatment for 6 weeks with either methylcysteine (1200 mg daily in Week 1, 800 mg daily in Week 2, then 600 mg daily) or with identical placebo tablets on the same regimen. During the post-treatment period, all patients returned to a single-blind placebo regimen (6 tablets daily) for a further 14 days. Assessments were made at the start, at regular intervals during the trial, and at the end of the post-treatment period, of subjective and objective measures of clinical response, and measurements of pulmonary function and certain physico-chemical properties of sputum. The results showed that methylcysteine increased sputum volume, reduced the viscidity of sputum, and significantly improved the subjective assessments of ease of expectoration and severity and frequency of cough, leading to a definite improvement in the patients' clinical state. No side-effects of clinical significance were reported and no abnormalities were found in any of the haematological, hepatic and renal function tests carried out.

Adult↗
PubMed1978

Metabolic and pharmacokinetic studies on Bamifylline. A review.

The metabolic fate and pharmacokinetics of Bamifylline have been investigated by high performance liquid- and gas-chromatography techniques and radio-isotopic methods in several experiments following oral and intravenous administration of single and repeated doses of 300 mg, 600 mg and 900 mg of this drug. The 300 mg single- and multiple-dose experiments were performed by comparing Bamifylline with 200 mg of Theophylline within the confines of controlled double-blind randomized cross-over studies. Bamifylline is catabolized into several closely related compounds and into sulpho- and glucurono-conjugates of an hydroxylated derivative. Its metabolites are rapidly and extensively excreted via the kidneys and the liver. Only the unchanged Bamifylline has been recorded in the blood following administration of the radio-labelled parent compound. Bamifylline achieves peak plasma levels more rapidly than Theophylline. The half-time of Bamifylline plasma concentrations ranges from 1.5 hours to 2.0 hours, which is appreciably shorter than that of Theophylline which exceeds four hours. By further contrast the distribution volumes of Bamifylline are three to ten times larger than those of Theophylline. No evidence of cumulation has been found in blood following the repeated administration off doses as high as 900 mg administered at intervals of eight hours.

Adult↗
PubMed1978

Coagulation factors in opposed and unopposed oestrogen treatment at the climacteric.

Laboratory tests of blood coagulation and platelet activity were undertaken in fifty-two climacteric patients who received cyclical oestrogen regimens for six consecutive months, following which they were given cyclical sequential oestrogen/progestogen regimens for periods ranging from fifteen months to twenty-seven months. The cyclical sequential regimen employed was determined by the dosage of oestrogen prescribed during the initial six-month period: norethisterone (2.5 mg or 5.0 mg) on days sixteen to twenty-one of cyclical treatment with oestrone piperazine sulphate or conjugated equine oestrogens, and DL-norgestrel (0.5 mg daily) from day twelve to day twenty-one of cyclical oestradiol valerate treatment. The results suggest that the addition of a progestogen to the cyclical oestrogen treatment does not modify blood coagulation factors or platelet aggregation.

Blood Coagulation↗
PubMed1978

Endometrial factors under treatment with oestrogen and oestrogen/progestogen combinations.

In a continuing prospective study, uterine curettage was undertaken on sixty-four patients attending a Menopause Clinic prior to consideration of gonadal hormone therapy. Two of these patients (3.1%) were found to have endometrial hyperplasia, and subsequently they were not given gonadal hormone therapy. Sixty-two patients with normal endometrium at pre-treatment curettage received cyclical oestrogen regimens or sequential oestrogen/progestogen treatments. Four (30.8%) of the thirteen patients in receipt of cyclical 'high-dose' oestrogens developed cystic glandular hyperplasia, whereas none of the patients taking either cyclical 'low-dose' oestrogens (thirty patients) or cyclical-sequential oestrogen/progestogen regimens (nineteen patients) developed endometrial hyperplasia. Among the patients with a normal endometrium, both before and during cyclical gonadal hormone therapy, regular withdrawal bleeding was experienced by thirty-two patients (51.6%). Breakthrough bleeding occurred in nine (14.5%), while twenty-one patients (33.9%) had no vaginal bleeding. Of the four patients with normal endometrium at pre-treatment curettage who subsequently developed endometrial hyperplasia during cyclical 'high-dose' oestrogen therapy, regular withdrawal bleeding was experienced by two patients, and in one of these breakthrough bleeding also occurred. Furthermore, in the four patients who developed endometrial hyperplasia, this condition occurred within six months in two patients and within 9 and 10 months respectively in the remaining two. In the nineteen patients receiving cyclical sequential oestrogen/progestogen regimens, all had regular withdrawal bleeding, while one patient had breakthrough bleeding during sequential therapy. It is concluded that in those climacteric patients who present with severe menopausal symptoms which necessitate the administration of high-dose oestrogen regimes it is necessary either to undertake both pretreatment uterine curettage or to add a progestogen to the oestrogen in a sequential regimen.

Climacteric↗
PubMed1976

Evaluation of tolmetin in the treatment of arthritis: open and controlled double-blind studies.

In a 6-week open study in 24 patients with rheumatoid arthritis, tolmetin was shown to have analgesic and anti-inflammatory activity at daily doses in excess of 1200 mg per day and produced statistically significant reductions in overall joint pain, walking time and articular index. The drug was well tolerated, but 2 patients were withdrawn because of persistent indigestion and 1 because of an urticarial type rash. In a double-blind crossover comparison against indomethacin and placebo in 22 patients, 1400 mg tolmetin daily showed efficacy comparable with that of 150 mg indomethacin daily. Few side-effects were reported and did not necessitate any patients being withdrawn.

Adult↗
PubMed1975

Long-term study of indomethacin and alclofenac in treatment of rheumatoid arthritis.

Indomethacin and alclofenac were compared for 13 months under double-blind conditions in 109 patients with active, classical, or definite rheumatoid arthritis at a relatively early stage of the disease. Both indomethacin and alclofenac were clearly effective: most patients either improved or remained as well controlled as on entry. Alclofenac proved the more effective drug, however, producing a significantly greater reduction in morning stiffness, articular index, and erythrocyte sedimentation rate, and only in the alclofenac-treated group did functional capacity improve and latex-agglutination titres diminish. Comprehensive laborabory tests showed no significant deviation from normal which could have been attributed to either drug.

Administration, Oral↗
PubMed1975

A study of the influence of various antirheumatic drug regimens on serum acute-phase proteins, plasma tryptophan, and erythrocyte sedimentation rate in rheumatoid arthritis.

In patients with rheumatoid arthritis neither indomethacin nor aspirin influenced the levels of the erythrocyte sedimentation rate (e.s.r) or serum acute-phase proteins fibrinogen, haptoglobin, C-reactive protein and alphaI acid-glycoprotein). Treatment with D-penicillamine, sodium aurothiomalate, or alclofenac produced a significant reduction both in acute-phase protein levels and in e.s.r. Each of the drugs displaced L-tryptophan from plasma proteins in vivo but withdrawal of indomethacin and aspirin was followed immediatley by excessive binding of this amino acid to circulating proteins:this phenomenon was not observed when alclofenac, sodium aurothiomalate or D-penicillamine were withdrawn. It has been demonstrated that disease activity in rheumatoid arthritis is reflected in acute-phase protein concentrations and in the extent to which L-tryptophan is bount to plasma protein. It is suggested that drugs which profoundly affect these parameters provide not only symptomatic relieft but also possible beneficial effects upon the disease process itself.

Adult↗