Pharmatherapeutica最新文献

The effects of 5 mg bendroflumethiazide plus 15 mmol potassium chloride versus 50 mg hydrochlorothiazide plus 5 mg amiloride on blood pressure and serum electrolytes were investigated in a 12-week, open, randomized study with parallel treatment groups. Forty-five patients with previously untreated hypertension and 33 hypertensive patients previously treated with thiazides until 1 month before allocation to the present treatments, completed the trial. Systolic and diastolic blood pressures were reduced significantly during treatment with both drug combinations. Significant negative correlations between initial serum potassium levels and the thiazide-induced decrease were observed. Mean potassium concentrations decreased by 0.39 mmol/l with bendroflumethiazide/potassium chloride and by 0.30 mmol/l with hydrochlorothiazide/amiloride. It is concluded that both treatments were effective and well tolerated in controlling patients with mild to moderate hypertension, and that the difference in the mean serum potassium concentration between the two treatments was not statistically significant.

Sixty out-patients with acute or sub-acute irritable colon were randomly allocated to receive a single intravenous dose of 50 mg tiropramide, 50 mg trimebutine maleate or 10 mg octilonium bromide. Before and after injection, multiple colonic manometry was performed, monitoring tonus, intensity and frequency of sinusoid contraction waves, transitories and vibrations, as well as the voluntary contraction capacity. Significant variations in tonus were not observed with any drug, but, while tiropramide left unmodified the voluntary contractile ability, a significant inhibition was observed with trimebutine and octilonium. The overall power of spontaneous colonic contractions did not vary significantly with tiropramide, whereas some decrease was observed with trimebutine, and a substantial one with octilonium. Moreover, while with tiropramide and, to a lesser extent, with trimebutine there was a significant redistribution of muscular power so as to increase phasic propulsion waves and to decrease the ineffective transitory and vibrational contractions, with octilonium only a decreased wave amplitude was recorded without alteration of the frequency of transient spasms. Based on these observations, tiropramide was evaluated as being at least as effective an antispasmodic as octilonium and at least as effective a synchronizer as trimebutine, while setting itself aside from both reference drugs as it was the only one to act contemporarily as both an antispasmodic and a synchronizer.

Tenoxicam (20 mg/day) and piroxicam (20 mg/day) were compared in a double-blind, parallel group study over 4 weeks in 30 patients with ankylosing spondylitis. Both tenoxicam and piroxicam reduced spinal pain, but the improvement was greater with piroxicam. Tenoxicam and piroxicam were equally effective at improving duration of morning stiffness. Slight improvement was seen with other symptoms with both treatments. Patients were slightly more tolerant of piroxicam than tenoxicam and most patients elected to continue on their particular therapy at the end of the study.

After oral administration of a single dose of ofloxacin (100, 300 or 600 mg) to 13 healthy male volunteers in an open, randomized crossover study, concentrations of the unchanged drug were estimated at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a wash-out period of 1 week. Ofloxacin concentrations were determined using both high pressure liquid chromatography (HPLC) and a microbiological assay. The measurements obtained were compared by linear distribution independent regression, and were found to be equivalent, indicating no major metabolism of ofloxacin. Maximum serum concentrations (Cmax) of ofloxacin after administration of 100, 300 or 600 mg were, respectively, 1.0, 3.4 and 6.9 mg/ml (HPLC, median values). A linear relationship between Cmax and dose was demonstrated within the range tested (coefficient of correlation r = 0.88). The same applied to AUC0-28 (r = 0.98) and to urinary recovery of the drug (r = 0.98). Time to reach Cmax varied between 0.5 and 1.1 hours (median values), indicating rapid absorption of the drug. Biological half-life (t1/2 beta) was determined by fitting a two-compartment open model to the date: t1/2 beta was in the range 5.6 to 6.4 hours (HPLC, median values) and was not relevantly dose-dependent. Urinary concentrations of ofloxacin remained above 1 microgram/ml, i.e. above the minimum inhibitory concentrations (MIC90) for most bacterial strains at all dosages tested, for at least 36 hours after drug administration. General tolerability was good; no side-effects were reported.

A study was carried out to evaluate the efficacy and tolerance of oral nifedipine in hypertensive emergencies. Eleven consecutive patients with very high blood pressure requiring emergency reduction were included in the study. Nifedipine (10 mg) was given orally at 6-hourly intervals and blood pressure, pulse, serum electrolytes, urea, creatinine and uric acid were monitored. A reduction in blood pressure was noted within 10 minutes, with a significant reduction occurring within 30 minutes (reduction of systolic blood pressure by 8.11% and diastolic blood pressure by 9.38%). The maximum reduction in blood pressure occurred within 90 minutes (reduction of systolic blood pressure by 20.78% and diastolic blood pressure by 21.74%) and remained at this level for 4 hours, after which a mild increase in blood pressure was noted. At 6 hours, the reduction in blood pressure was 15.41% and diastolic reduction was 17.94%. The reduction in blood pressure was found to be directly correlated with the pre-treatment blood pressure. There was no significant alteration in the pulse rate or blood chemistry. No side-effects were noted during the study. It is suggested that oral nifedipine is a simple, effective and well-tolerated alternative to parenteral therapy in the management of hypertensive emergencies.

Thirty out-patients with gastric (8) or duodenal (22) ulcers were randomly assigned to receive a daily dose of 1.0, 1.5 or 2.0 g triletide over a period of 8 weeks. Endoscopic findings and overall clinical rating indicated that triletide effectively accelerated ulcer healing in a proportion of patients (73% of responders), with a trend for better response at doses higher than 1 g/day, regardless of the ulcer location. Heartburn, epigastric pain and concomitant antacid consumption improved significantly in each dose group, but to a significantly greater extent in the highest dose group than in either mid-dose or low-dose groups. Tolerance of treatment was good at all dose levels, and no significant variations in routine haematology, haematochemistry or renal function tests were observed. It is suggested, therefore, that triletide provides an effective and well-tolerated new means to promote ulcer healing, both gastric and duodenal, with easily graded symptomatic relief by modifying the daily dose.

Six healthy volunteers were administered a single 1 g dose of triletide, orally, and blood concentrations of the parent drug determined by high pressure liquid chromatography over a 10-hour period. Analysis of both individual and pooled data indicated that triletide was well absorbed after oral administration, with a lag time of 0.3 hours and the blood peak was reached after about 1.1 to 1.3 hours. Metabolization to desmethyl, desacetyl, desmethyl-desacetyl and hydroxylated derivatives plays a major role in the biotransformation of the drug and thus in its disappearance from blood, the distribution half-life being about 1 hour. Elimination half-life ranged about 5 hours, thus suggesting a dosage schedule of 3-times daily for loading, while for maintenance a twice-daily schedule appears also suitable. The existence of deep compartments and, therefore, risks of accumulation appear to be excluded.

Ninety-three patients scheduled for various elective surgical procedures were divided into three equal groups and had induction of anaesthesia with either thiopentone (5 mg/kg), thiopentone (5 mg/kg) plus gallamine (0.3 mg/kg), or with flunitrazepam (0.03 mg/kg). Four minutes after induction they received a bolus intravenous injection of succinylcholine (1 mg/kg). Intra-ocular pressure was measured before and after induction, and approximately 1 minute after succinylcholine. It was found that flunitrazepam prevented the increase in intra-ocular pressure better than thiopentone plus gallamine. In both these groups, the subsequent intravenous administration of succinylcholine slightly increased the pressure but to levels below that noted before anaesthesia was induced. However, intra-ocular pressure was significantly increased above baseline levels when succinylcholine was injected after induction with thiopentone alone. Flunitrazepam is recommended, therefore, as a possible alternative for thiopentone-gallamine induction with succinylcholine when an increase in intra-ocular pressure must be prevented.

A study was carried out in 30 out-patients with endoscopically confirmed active, benign gastric or duodenal ulceration to assess the comparative effectiveness and tolerance of treatment with triletide, a new synthetic tripeptide with anti-ulcer properties, with that of conventional antacids. Patients were allocated at random to receive treatment with either 1.6 g aluminium hydroxide and 1.6 g magnesium hydroxide per day or the antacids plus 1.5 g triletide per day over a period of 8 weeks. Heartburn and epigastric pain, monitored every other week, were significantly relieved by both treatments, but to a significantly greater extent (70% vs 20% on average, p less than 0.01) and significantly faster (p less than 0.01) in the presence of triletide. Endoscopic control showed that the patients who had triletide experienced complete healing in a significantly greater proportion (73% vs 27%, p less than 0.02) than those who had antacids only. The efficacy of treatments was the same, regardless of the actual ulcer location. Routine haematology and haematochemistry findings were unaffected by either treatment, and subjective possible side-reactions were limited to constipation (9 complaints overall) which is a well-known side-effect of antacid treatment. It would appear, therefore, that triletide is at least as well tolerated as antacids, while promoting the healing of peptic ulcers in a significantly greater proportion of patients and easing symptoms significantly faster and to a greater extent than antacids alone, regardless of the ulcer location.

A double-blind study was carried out in two parallel groups of patients with mild to moderate hypertension to assess the efficacy and tolerance of the combination 20 mg penbutolol plus 3 mg piretanide in comparison to 40 mg penbutolol alone over a period of 6 weeks. Active drug treatment in the 51 patients studied was preceded by a 2-week period of placebo. The results showed that in both groups there was an effective reduction in systolic and diastolic blood pressure compared with initial levels. Although there was no significant difference between the groups, the normalization of diastolic blood pressure (less than 95 mmHg) was achieved in 70% of the patients receiving the combination and in 59% of the patients treated with penbutolol alone. Pulse rate decreased in both groups, body weight only in the combination group. The biochemical and haematological parameters showed no clinically relevant changes during treatment with either drug regimens. Minor side-effects definitely or probably associated with the treatment were observed in both groups but were generally mild and did not interfere with treatment. No patient withdrew prematurely from the trial.