[Prolonged action nitrates in stable angina pectoris]. / Langtidsvirkende nitrater ved stabil angina pectoris.

A randomized double blind comparison of transdermal nitroglycerin and isosorbide dinitrate tablets was conducted in 100 men with stable angina pectoris. Subjective and objective effects were virtually identical for both regimens (number of angina attacks/nitroglycerin consumption and exercise ECG test variables). The pattern of side effects was also similar for both drugs. A considerable dissociation was observed between subjective effects and effects measured by ergometer test in the individual patient. Lack of both subjective and objective effects--i.e. nitrate tolerance--was observed in approximately one fourth of the patients, and was not prevented by a twelve-hour dosing interval on isosorbide dinitrate nor a six hour transdermal nitroglycerin-free interval. Our data lends credence to the notion that the effects of long-acting nitrates in daily life and the effects measured during stress testing may involve different mechanisms.

Optimal assessment of gastrointestinal side effects induced by non-steroidal anti-inflammatory drugs. Endoscopic lesions, faecal blood loss, and symptoms not necessarily correlated, as observed after naproxen and oxindanac in healthy volunteers.

Gastrointestinal side effects caused by naproxen and oxindanac (a developmental non-steroidal anti-inflammatory drug) were compared by combined endoscopy and determination of faecal blood loss in 16 healthy male volunteers in a randomized, double-blind, crossover study. Individual daily faecal blood loss was determined by means of 51Cr-labelled erythrocytes. Gastroduodenoscopy was performed before and after administration of naproxen, 750 mg/day, and oxindanac, 600 mg/day, for 1 week each. A washout period of at least 3 weeks was inserted between drug periods. Visual analogue scales (VAS) were used for endoscopic assessment of lesions and subjective complaints. Mean faecal blood loss increased from a base line 0.48 ml/24 h to 1.59 ml/24 h with naproxen (p less than 0.01) and from 0.56 ml/24 h to 1.31 ml/24 h with oxindanac (p less than 0.01). VAS scores for gastroduodenal lesions increased significantly with both drugs. Naproxen caused a significantly greater increase than oxindanac (p less than 0.05). There was no correlation between gastrointestinal blood loss and endoscopic findings. Subjective symptoms were correlated to faecal blood loss with naproxen, but not to endoscopic findings. No such correlations were observed for oxindanac. Naproxen caused a significant prolongation of bleeding time (p less than 0.01), whereas the increase caused by oxindanac was not significant (p = 0.09).

The anti-oedematous efficacy of oxindanac equals that of paracetamol in acute postoperative inflammation; are weak cyclooxygenase inhibitors more effective than strong inhibitors?

In a double-blind crossover study, the clinical anti-oedematous efficacy was compared of a weak cyclooxygenase inhibitor oxindanac 200 mg thrice daily in a controlled clinical trial procedure with paracetamol 1 g thrice daily as a positive control involving objective measurement of acute soft tissue oedema. Paracetamol is a weak cyclooxygenase inhibitor which reduces acute postoperative tissue oedema by 30% compared to a placebo. There was no significant (p = 0.81) difference between oxindanac and paracetamol with respect to anti-oedematous activity. The present finding is discussed in view of previous results obtained in controlled trials with several other anti-inflammatory drugs, using similar objective methodology as the present one. It is proposed that non-steroidal anti-inflammatory drugs acting solely by strong inhibition of cyclooxygenase need not be optimal anti-oedematous drugs. Reasons for this proposal are discussed.

Factors influencing the sample size, exemplified by studies on gastroduodenal tolerability of drugs.

The necessary number of subjects to be included in a clinical trial depends on different factors. Exemplified by clinical trials on gastroduodenal tolerability of NSAID, we show how the sample size increases when the significance level decreases, the detection level increases, or the clinically relevant difference decreases. The sample size also increases when the trial design is changed from a cross-over to a parallel-group design. It is concluded from an ethical and statistical point of view that the sample size must be calculated when planning a study.

Effect of diclofenac and naproxen on gastroduodenal mucosa.

The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclofenac, 100 mg/day, for 1 wk was investigated in 14 subjects in a double-blind randomized crossover study. Endoscopic examination of the gastroduodenal mucosa was carried out before and after each drug with regard to gastritis and hemorrhagic and erosive lesions. A 20-cm visual analogue scale was used for grading severity of mucosal changes. Naproxen caused statistically significant increases inmedian scores for all 3 variables, and 10 subjects showed a score increase in at least 1 variable; reaction to diclofenac occurred in only 4 subjects and the changes in median scores were not significant.

Absorption of rifampicin in gastrectomized patients. Effect of meals.

Rifampicin absorption was studied in six gastrectomized and six non-gastrectomized tuberculous patients who had been on continuous rifampicin therapy for more than 4 weeks. A dose of 450 mg was given on two occasions, first immediately after breakfast and, 2 days later, 1 h before breakfast. In all the gastrectomized and control patients a serum level well above the MIC for M. tuberculosis (0.2-0.5 microgram/ml) was achieved irrespective of whether rifampicin was administered after the meal or during fasting. Gastrectomized patients tended to have more delayed serum concentration peaks postprandially than when fasting. The differences in absorption were not statistically significant, and the serum concentrations remained above the MIC for M. tuberculosis for similar lenghts of time. Individual serum concentrations varied greatly, and this variation may represent a greater problem in the routine monitoring of rifampicin serum levels than administration of the drug with food.