Showing papers on "Tolerability published in 1977"

Diflunisal: a review of pharmacokinetic and pharmacodynamic properties, drug interactions, and special tolerability studies in humans.

Abstract: 1 In the fasting state, peak plasma levels of diflunisal were achieved within 2 hours. The drug was not metabolized and almost totally excreted in the urine as unchanged or conjugated drug. The terminal plasma half-life was approximately 8 hours. These results support a twice daily dose regimen. 2 During multiple dose administration the time required to achieve steady-state plasma levels varied with the dose. A dose regimen of 125 mg twice daily required 2-3 d, whereas a regimen of 500 mg twice daily required 7-9 d to reach a steady-state plasma level. 3 Clinically effective doses of diflunisal decreased the urinary excretion of the major prostaglandin E metabolite, 7α-hydroxy-5,11-diketotetranorprostane-1,16-dioic acid, and exhibited significant uricosuric activity. These same doses did not seem to cause tinnitus, nor did they significantly alter gastrointestinal blood loss, affect blood glucose, bleeding time, or platelet function. 4 Clinically significant drug interactions may be anticipated during concomitant administration with at least one oral anticoagulant (acenocoumarol), but probably not anticipated during the coadministration of oral antidiabetic agents, thiazide diuretics, and non-steroidal anti-inflammatory/analgesic agents. 5 Clinical and laboratory data accumulated during these studies indicated that diflunisal was well tolerated.

Double-blind controlled study in phobias and obsessions.

Abstract: A double-blind between-patient study is described which was aimed at assessing the efficacy and tolerability of clomipramine (Anafranil, Geigy Pharmacetuicals) in clinically depressed patients with obsessive-compulsive and phobic psychopathological traits. Twenty patients of either sex aged between 18 and 65 years were randomly allocated to treatment with clomipramine (50 mg twice daily) or to treatment with an identical placebo. Patients were assessed at the commencement of the study and at two-weekly intervals over the six-week duration of the trial. By the methods of assessment used, clomipramine proved to be highly statistically significantly superior to placebo.

Diftalone: a new non-steroidal anti-inflammatory agent: comparative study with phenylbutazone in the treatment of rheumatoid arthritis.

Abstract: A double-blind study was carried out to compare the effectiveness and tolerability of diftalone and phenylbutazone in thirty patients with classical or definite rheumatoid arthritis, randomly distributed between the two treatment groups. Both drugs were administered according to a progressively decreasing daily dosage schedule: 1,000 mg during the 1st week; 750 mg the 2nd week and 500 mg from the 3rd week on for diftalone; 400 mg, 300 mg, and 200 mg daily for the 1st, 2nd and from the 3rd week on respectively for phenylbutazone.The study lasted twelve weeks. The clinical controls and laboratory tests were performed weekly up to the 8th week, while the final evaluation was made at the end of the 3rd month.Twelve patients in the group receiving diftalone and fourteen in the phenylbutazone group completed the trial.Clinical improvement was observed in both groups. Effectiveness was somewhat more evident in the diftalone group. Tolerability was acceptable for both drugs, although the diftalone patients showed...

Antihypertensive effect and tolerability of metoprolol during long-term treatment: a multicentre study.

Abstract: One hundred and forty-seven patients with essential hypertension participated in this multicentre study. The results indicate that metoprolol in a dosage of 150-450 mg daily is an effective and well tolerated therapy both in patients previously untreated and in patients unsatisfactorily treated with other antihypertensive agents.

A comparison of various clomipramine (Anafranil) dosage regimes.

Abstract: This study was a multicentre general practitioner trial comparing four dosage regimes of clomipramine (Anafranil, Geigy Pharmaceuticals): 10 mg t.d.s., 30 mg o.n., 25 mg t.d.s. and 75 mg o.n. This paper concerns the clinical results obtained using a series of twelve visual analogue scales completed independently by doctor and patient. Also side-effects, recorded on a standard list of unwanted effects of tricyclic antidepressants, were studied. Very few statistical differences were found between the dosage regimes, and they were difficult to interpret clinically. It was concluded that although 25 mg t.d.s. was most effective, 30 mg o.n. was probably the best compromise in terms of efficacy and tolerability.

Pilot study of two adriamycin-based regimens in patients with advanced malignant lymphomas.

Abstract: Forty-two patients with advanced malignant lymphomas, all of whom had failed at least one prior course of chemotherapy, were treated with one of two new combination chemotherapy regimens to determine patient tolerability. Twenty-seven patients received regimen 1, after which this study was discontinued, and subsequently 15 additional patients were treated with regimen 2. Regimen 1 (BAP) consisted of BCNU and adriamycin administered iv on Day 1 and prednisone administered orally on Days 1--5 with cycles repeated at 21-day intervals. Regimen 2 (VAP) consisted of VP-16-213 given iv on Days 1 and 2, adriamycin given iv on Day 3, and prednisone given on Days 3--7 in a schedule designed to produce cell cycle synchronization; cycles were repeated at 21--28-day intervals. Both regimens were, in general, well tolerated. Reversible bone marrow depression was the major toxic reaction observed. Nine of 27 patients treated with regimen 1 and five of 15 patients treated with regimen 2 experienced objective tumor regressions. Tolerable dosage levels of both regimens have been defined for future clincial trials.

Ibuproxam and ibuprofen. A pharmacological comparison.

Abstract: The anti-inflammatory, analgesic and antipyretic effects and the tolerability of 2-(4-isobutylphenyl)-propionic acid (ibuprofen) were compared with those of its derivative 2-(4-isobutylphenyl)-propiohydroxamic acid (ibuproxam, Ibudros Our experiments show that the interfering action of the two drugs with the reactive processes of the tibio-tarsic articulation, brought about by carrageenin, serotonin, dextrane and formalin is of the same intensity Also, the analgesic activity is perfectly consistent with the antipyretic one However, the tolerability of the two molecules is different; the acute toxicity is consistent in the case of the single parenteral administration and it differs in the case of a single or repeated oral treatment When used under these conditions, ibuproxam is considerably less damaging to the gastroenteric tube than is ibuprofen The hypothesis is put forth that the greater tolerability of ibuproxam is due to its pharmacokinetics: it is, as such, little or not toxic for the mucous membrane of the digestive apparatus, and it progressively releases ibuprofen, whose concentrations in the blood would remain below those levels that cause systemic lesions in the gastroenteric tract

Fentiazac as a Therapeutic Aid in the Treatment of Tuberculosis

Abstract: The authors point out the clinical usefulness and optimal tolerability of Fentiazac in patients suffering from tuberculosis and whose condition requires therapeutic intervention with non-steroid an...

Butazolidin suppository medication in rheumatism; a clinical study in general practice.

Abstract: One hundred and seventeen patients with various rheumatic conditions were admitted by eighteen general practitions to a multicentre open clinical trial of the acceptability, effectiveness and tolerability of Butazolidin Suppositories. Dosage was one or two suppositories (= 250 mg or 500 mg phenylbutazone) per day for up to eight weeks. Of the 117 patients entered onto the register for the study, 10 patients refused suppository medication and 8 had local conditions contra-indicating their use. Of the 99 patients starting the trial proper, half had excellent symptomatic relief and tolerance. Sixteen patients discontinued because of poor response. The remainder (34) whilst having significant improvement as shown by mean symptom scores, discontinued treatment. The majority who discontinued did so because of minor local discomfort or minor gastric symptoms, suggesting that acceptability of medication was at least as important as intolerance. No patient had a serious or persistent adverse effect. Comparison with previous studies suggests that gastro-intestinal tolerance to phenylbutazone is improved when it is administered by suppository.

Clinical study with bromperidol, a new butyrophenone derivative.

Abstract: 20 psychotic - predominantly schizophrenic - patients underwent treatment with the new butyrophenone derivative bromperidol for a period of 4 weeks; the drug was administered in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. 19 patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. The therapeutic value of this new substance will be demonstrated by a double-blind study.

Clinical investigation of halopredone acetate, a new topical steroid, in dermatology. Controlled study.

Abstract: 17,21-Bis(acetyloxy)-2-bromo-6beta,9-difluoro-11beta-hydroxypregna-1,4-diene-3,20-dione (halopredone acetate; Topicon) cream, a new synthetic corticosteroid for topical use, has been evaluated against betamethasone valerate by means of double-blind sequential study, where the patients, mainly affected with psoriasis, presented symmetrically located lesions which were treated with either the new drug or the reference cream so that each patient could serve as his own control. Activity and tolerability of the two preparations were equivalent. This equivalence is particularly significant when bearing in mind that the concentration of the active principle (0.01%) contained in the halopredone acetate cream is one of the lowest employed so far and 10 times lower than that of the reference steroid (betamethasone valerate 0.1%). A second open trial, made in 30 patients suffering from psoriasis, confirmed the positive anti-inflammatory properties which the new substance had already displayed during the previous pharmacological tests.

Maprotiline (Ludiomil) in depression: a multicentre assessment of onset of action, efficacy and tolerability.

Abstract: Although open studies have a built-in bias of optimism the results from this study, made valid by the large numbers of patients involved, support the findings reported with smaller numbers in controlled series of studies showing an early onset of action with maprotiline (Ludiomil). The method used in this study to detect unwanted effects indicates that maprotiline is well tolerated. In summary, the efficacy of once daily dosage, the good response in differing types of depressive illness, the early onset of effectiveness without serious side-effects in a wide age range of patients suggests that this drug will be a useful addition for the treatment of depressive illness in general practice.

[Assessment of the therapeutic effect of Trental 400. Double-blind study in geriatric patients with circulatory disorders].

Abstract: A double blind trial was performed in a geriatric unit in order to evaluate efficacy and tolerability of Trental 400 (400 mg Pentoxifylline per tablet) against a comparative formulation (2,4 mg adenosine per tablet) in 36 patients displaying signs of peripheral vascular disease and in 16 patients with symptoms of cerebrovascular disorders. 3 tablets were administered daily over a period of three months. Trental 400 proved to be significantly more effective in either indication group. Based on the observed good tolerability and pronounced efficacy Trental 400 can be considered as an easy to handle therapeutic tool for the long term treatment of symptoms resulting from peripheral and cerebral vascular disorders.

A comparative study of maprotiline (Ludiomil) and viloxazine in the management of depressed patients in general practice.

Abstract: A double-blind, comparative, multicentre study comparing the efficacy and tolerability of maprotiline (Ludiomil) and viloxazine as antidepressants in general practice usage is described. Progress was measured at weekly intervals over the 4-week trial duration using a modified Hamilton Rating Scale and patient self-assessment visual analogue scales. A total of 127 patients were randomized into two groups; 63 patients being allocated maprotiline and 64 patients being allocated viloxazine. Of the patients receiving maprotiline, 12 withdrew during the course of the study compared to 9 patients receiving viloxazine. Maprotiline appeared to be superior to viloxazine on the sleep and sadness scales and some evidence to show it to be better also on the tension scale. Whilst the trend favoured maprotiline, the two drugs did not appear to be significantly different on either the doctors' or the patients' assessments. There was little to choose between the drugs in terms of side-effects or ultimate patient tolerability and preference.