Pharmatherapeutica最新文献

An assessment of the efficacy and tolerability of zuclopenthixol dihydrochloride tablets in the treatment of acute psychotic episodes was undertaken in 63 patients in an open multi-centre study. Most patients prior to entering the study had received other neuroleptic drugs, but with inadequate effect. During the 10-week study, the dosage of zuclopenthixol dihydrochloride tablets could be adjusted to obtain optimum clinical benefit. The majority of patients received 20 to 75 mg daily (range 10 to 150 mg daily) at the start of the study and later, for most of those patients successfully treated, the dosage was 20 to 55 mg daily. Assessments before and during treatment utilized the BPRS and CGI rating scales and a check-list of side-effects. A successful response to treatment was achieved in 70% of 50 patients with schizophrenia or schizophreniform psychoses and in 69% of 13 patients with mania or hypomania. Almost half (30) of the patients studied had a successful response within 4 weeks of starting treatment and some after only 1 week of treatment. All patients but 1 had either no side-effects or side-effects not overtly affecting performance.

A single-blind trial was carried out in 18 patients with moderately severe hypertension to investigate the efficacy of the angiotensin-converting enzyme inhibitor captopril in combination with the calcium antagonist verapamil after treatment with captopril alone had failed to achieve satisfactory control. For the first 2 weeks of the study, patients received 50 mg captopril twice daily, then 50 mg captopril plus 160 mg verapamil twice daily for 4 weeks, followed by 160 mg verapamil twice daily for a further 4 weeks. The double-dummy technique was used with placebo tablets given during the first and last treatment periods. Blood pressure and heart rate measurements in the supine and standing position were made at 2-week intervals throughout the study. Analysis of the results from the 13 patients who completed the trial protocol showed that the two drugs in combination produced significant reductions (p less than 0.01) in both supine and standing blood pressures compared with captopril alone, but a significant reduction (p less than 0.02) only in diastolic blood pressure compared with verapamil alone. Heart rate was not changed significantly throughout the study. Only 1 patient was withdrawn because of side-effects, although on questioning constipation, in particular, proved to be a problem in many.

A 6-month, double-blind, controlled, randomized, parallel study was performed to compare the efficacy and tolerance of nabumetone (1000 mg at bedtime) with naproxen (250 mg twice daily) in the treatment of osteoarthritis. Five efficacy parameters were evaluated: patient's assessment of overall osteoarthritis activity and pain, physician's assessment of overall osteoarthritis activity and pain, and physician's assessment of pain with respect to a defined activity. All 40 patients entered (20 in each group) were available for evaluation of tolerance and 36 patients for efficacy analysis (18 in each group). The efficacy results revealed significant improvement in all five parameters for each medication except measurement of pain with respect to a defined activity for naproxen (p less than 0.07). The frequency of possible or probable drug-related adverse experiences was high for both drugs. However, only 1 patient left the study because of a probable drug-related adverse experience (abdominal pain in a nabumetone patient). Six nabumetone and 4 naproxen patients dropped out of the study because of lack of efficacy. The results indicate that nabumetone and naproxen have comparable efficacy and tolerance at the dosage used, and suggest that a single night-time dosage of nabumetone may be a convenient and useful treatment for osteoarthritis.

A randomized study was carried out in 195 out-patients, due to undergo large bowel radiological examination, to compare the efficacy, patient acceptance and incidence of side-effects of a commercially-available bowel evacuant kit (magnesium citrate oral solution, phenolphthalein tablets and a bisacodyl suppository) and castor oil with enemas. Overall evaluation by a radiologist of large bowel preparation, based on post-barium evacuation X-rays, was satisfactory in more than 98% of patients while bowel cleanliness, as determined by the ability to detect a 1 cm lesion, was adequate in 95% of patients using either preparation. Patient acceptance was in favour of the commercial preparation in that fewer patients using it found the procedure uncomfortable or indicated a preference for another evacuant than did those prepared with castor oil and enemas.

A double-blind, double-dummy study design was used to compare the efficacy and tolerance of naproxen with that of pirprofen in the treatment of osteoarthritis. Sixty patients were assigned randomly to receive either 500 mg naproxen twice daily or 400 mg pirprofen twice daily for 4 weeks. Both groups were similar in all respects except age, which was significantly greater in the naproxen-treated patients than in the pirprofen-treated patients. Both treatments yielded statistically significant improvement in duration of stiffness after inactivity, global pain, pain on full passive movement, pain during a selected activity, and physicians' and patients' assessments of overall arthritic condition. There were no significant differences between the two groups in either the incidence or the severity of adverse effects of the drugs, most of which involved gastro-intestinal disturbances. Both medications were shown to be well tolerated, acceptable, and effective for treating osteoarthritis.

A total of 6258 patients seen in general practice complaining of low mood with or without associated somatic symptoms was studied. The mean patient entry score on the Montgomery-Asberg Depression Rating Scale (MADRS) was 29.69 (moderately severe depressive disorder). Three-quarters (73%) of the patients were female, average age was 46.1 years, and a reactive element was considered to be present in 43%. Patients received fluvoxamine, a novel anti-depressant, over a treatment period of 6 weeks, dosage starting at either 50 or 100 mg at night increasing after the first week, if necessary, to a maximum of 300 mg per day. Results were analyzed for 5625 patients. Efficacy of treatment was assessed using the MADRS, Psychosomatic Symptom Scale and Clinical Global Impression scales. During treatment, there was a marked improvement in mood and a parallel improvement in somatic symptoms; there was no difference in overall response between those with or without somatic symptoms. By Week 6, patients had improved by approximately 65%, with suicidal ideation being most marked at 81%. Patient compliance was good, the most commonly reported unwanted effect being nausea. In overdoses up to 2 g fluvoxamine no lasting toxic effects were observed. In an 'elderly' sub-group of 1096 patients aged 60 years and over, efficacy and the incidence of unwanted effects were similar, but the drop-out rate due to intolerance was greater than in the younger age sub-group.

A double-blind, multi-centre study was carried out in general practice in 76 patients with infected eczema and 43 with impetigo to assess the effectiveness and acceptability of treatment with 1% hydrocortisone plus 0.5% potassium hydroxyquinoline sulphate cream compared with that of 1% hydrocortisone plus 2% miconazole nitrate cream. Patients were allocated at random to receive treatment with one or other preparation, applied twice daily, over a period of 2 weeks. Assessments were made of total symptom severity scores on entry and at the end of each week, as also were bacteriological investigations. The results showed that both combinations produced marked clinical and bacteriological improvement or cure in approximately 90% of patients with infected eczema and the success rate was similar with each preparation. In the case of patients with impetigo, hydrocortisone/potassium hydroxyquinoline sulphate proved significantly more effective than the other combination, the success rates being 92% and 74%, respectively. Patient assessment of the two topical preparations in terms of greasiness, odour and staining showed that, whilst both were considered acceptable by most, there was a trend in favour of the hydrocortisone/potassium hydroxyquinoline sulphate cream. No systemic or local side-effects were reported.

A clinical trial on fenoverine was performed in two parts, one double-blind and one open. In the double-blind segment, 69 patients with chronic gastro-intestinal spasmodic conditions were allocated, according to a pre-set randomization table, to receive orally 3 daily doses of fenoverine (100 mg; 35 patients), trimebutine (150 mg; 14 patients) or placebo (20 patients) during an average of 8 days. In the open assay, 60 similar patients were treated during an average of 10 days with 100 mg fenoverine, orally, 3-times daily. Clinical efficacy was evaluated on the grounds of complete or almost complete remission of all symptoms and signs associated with the spasmodic condition. In the double-blind segment, 66% of patients given fenoverine experienced remission, a significantly higher proportion than those who had placebo (40%). The results with trimebutine (71%) could not be statistically differentiated from those of either fenoverine or placebo. In the open segment, 72% of patients experienced remission with fenoverine, thus showing an overall effectiveness in 70% of the total 95 patients who had such treatment. In neither study could a significant influence of spasm localization be shown on the clinical efficacy of fenoverine. Fenoverine also exerted an unexpected, though clinically interesting, anti-emetic action: of the 14 patients reporting vomiting on entry, 12 (86%) responded positively to fenoverine, whereas none responded out of the 3 who had placebo. Possible side-reactions were limited with fenoverine: there were only 17 (18%) complaints, mainly dry mouth, of which 6 were very mild.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-three optimally digitalized patients with congestive heart failure completed a 4-week treatment period with a fixed-drug association of 20 mg furosemide plus 50 mg spironolactone. Eleven patients responded with a 75% decrease in cardiac failure score on a daily dose of 1 capsule of the combination. The remaining 12 patients were initiated on the same dose, but needed, at the end of the first 14 days, an additional capsule (making a daily total of 40 mg furosemide and 100 mg spironolactone) over the next 2 weeks. On this dose, the patients achieved an average reduction of 52% in their cardiac failure score. There were no treatment failures. Electrolyte abnormalities and side-effects were not observed. The combination product, in a daily dose of 1 or 2 capsules, was found useful and well tolerated in the management of congestive heart failure.

The pharmacokinetics of isoxicam, a new non-steroidal anti-inflammatory drug, were studied in 20 osteoarthritis patients with varying degrees of renal insufficiency. A wide variation in pharmacokinetic parameters was seen between individuals but there was no suggestion that renal function influenced pharmacokinetics. Steady state plasma isoxicam concentrations varied from 20 micrograms/ml to 130 micrograms/ml, while the plasma half-life varied from 23 hours to 58 hours. Despite a reduction in urinary prostaglandin E2 excretion, isoxicam administration did not alter renal function over a 4-week period.