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OBJECTIVE: To study the pharmacological interaction between a dihydropyridine derivative (nifedipine slow release 20 mg) and inhibition of the renin-angiotensin system (benazepril 10 mg). DESIGN: Single application at intervals of 2 weeks in an open-label three-way cross-over design. SETTING: Institutional pharmacological unit. PARTICIPANTS: Nine healthy male volunteers. MAIN OUTCOME MEASURES(S): Blood pressure and heart rate were recorded in the supine position for 24 h as well as plasma drug levels, plasma angiotensin converting enzyme activity and active plasma renin concentration. RESULTS: Nifedipine increased active plasma renin two-fold and benazepril increased it five-fold. The combination of the two drugs accelerated the increase of active renin during the first 2 h after drug intake. Whereas no hypertensive effect could be detected after nifedipine or benazepril alone, a significant fall in systolic and diastolic blood pressure was observed for up to 9 to 12 h after the combination. The increase in heart rate induced by nifedipine was minimized by the addition of benazepril. There was no interaction between the pharmacokinetics of benazeprilate and nifedipine which would explain these pharmacodynamic effects. CONCLUSION: These results demonstrate that, in normotensive volunteers, the renin-angiotensin system contributes to mask the hypotensive effect of a single oral dose of dihydropiridine. The concomitant administration of a converting enzyme inhibitor discloses the hypotensive effect and limits the baroreflex-mediated increase in heart rate secondary to vasodilation.

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Nineteen patients receiving oxprenolol slow-release (SR) 160 mg (three patients) or 320 mg (16 patients) once daily for mild to moderate hypertension were treated with oxprenolol Oros 16/260 once daily for 3 weeks following a 2 week placebo wash-out period. Repeated dosing with both Oros and SR oxprenolol preparations, in comparison with placebo, significantly reduced supine systolic and diastolic blood pressures, and pulse rate at 24 h after dosing. Single Oros doses also significantly reduced pulse rate and diastolic, but not systolic, blood pressure at 24 h. The reduction in supine systolic blood pressure was greater during repeated dosing with oxprenolol SR than after a single dose of the Oros preparation. Control of supine diastolic blood pressure (less than or equal to 90 mm Hg) at 24 h after dosing was achieved in 13 out of 18 patients with oxprenolol SR (two out of three patients given 160 mg, and 11 out of 15 given 320 mg). Similar control was achieved in 11 out of 18 patients after a single dose of oxprenolol Oros, and in 13 out of 17 patients treated for 3 weeks. The mean percentage reduction in exercise heart rate (EHR) compared to placebo, at 24 h after dosing, was 16% following Oros treatment for 3 weeks, and 12% following SR administration. After a single dose of oxprenolol Oros EHR, was reduced by 9% at 24 h compared to placebo. At 3 weeks the Oros formulation was significantly better than the SR tablet at reducing EHR. Oxprenolol Oros 16/260 was effective over 24 h and well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

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To compare acute effects of nitroglycerin (0.8 mg sublingually), nifedipine (5 ng/kg/min i.v.) and metoprolol (0.15 mg/kg i.v.) on normal, ischemic and scarred myocardial segments in man, we performed simultaneous hemodynamic and radionuclide measurements of left ventricular functions. Sixteen patients with isolated left anterior descending (LAD) disease were studied at rest and during exercise. Nine patients had angina and exercise-induced ischemia (LAD stenosis) and seven patients had previous transmural myocardial infarction and no ischemic changes during thallium imaging (LAD occlusion). The effects of the drugs on regional ejection fraction of the involved anteroseptal region and the normal posterolateral area were compared. Global ejection fraction at rest did not change after nitroglycerin, increased after nifedipine and decreased after metoprolol. In patients with ischemia, the exercise ejection fraction improved after all drugs due to increased regional ejection fraction in ischemic segments: i.e., a regional antiischemic effect evidenced by improved regional function could be demonstrated with all three agents. Regional ejection fraction increased from 35.8 +/- 19.5% to 66.2 +/- 15.2% (+/- SD) after nitroglycerin (p less than 0.001), to 61.7 +/- 8.7% after nifedipine (p less than 0.001), and to 48.4 +/- 7.0% after metoprolol (p less than 0.01). In regions of myocardial scar, regional ejection fraction was not changed after any drug. In normal areas, regional ejection fraction remained unchanged after nitroglycerin and nifedipine, but decreased after metoprolol. Despite similar antiischemic effects of all three drugs, underlying hemodynamic mechanisms were quite different and may provide a rationale for combined forms of treatment. These results may help to select optimal drug combinations to improve myocardial performance in patients with chronic ischemic heart disease.

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40 women were treated for uncomplicated genital gonorrhoea, verified by culture, with a single oral dose of 1,200 mg rifampicin (Rimactan). The ages ranged between 15 and 51 years. In 33 patients that could be evaluated, the gonorrhoea was cured. In 8 of 18 patients the preexistent vaginal discharge improved. 4 women experienced six different side effects which were probably related to rifampicin. The 1,200-mg rifampicin oral one-dose treatment is a reliable, efficient, and well-tolerated therapy of uncomplicated gonorrhoea in women.

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The new semi-synthetic oral cephalosporin, CGP 9,000, has been evaluated in a large number of hospitalized patients with urinary infections. A total of 57 of these patients suffering from concomitant diabetes was matched with an equal number of non-diabetic patients. Patients were treated for 10 days with either 500 mg or 1.0 g CGP, or 1.0 g cephalexin. The predominant pathogens isolated were E. coli, Strep. faecalis, Proteus mirabilis and Klebsiella spp. Comparison of the results showed that the eradication rate was similar in diabetic and non-diabetic patients and there were no significant differences between the three treatment groups. There was a similar improvement in pyuria, and therapeutic response was equally as good in diabetic patients on 500 mg CGP 9,000 per day as in non-diabetic patients and in the other treatment groups. No unwanted effects on renal function were observed in the high-risk diabetic group.

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As long-term anticoagulant therapy with coumarin derivates like Sintrom becomes more and more important the question arises whether there is an interaction with a new drug like Ludiomil. An open, noncomparative trial was carried out with 20 patients receiving Sintrom (overall mean :3.0 mg/d, range :0 to 10 mg/d) for a period of 4 weeks, and in addition, during the second and third week Ludiomil (50 mg t. i. d.) orally. As a measurement of the efficacy of the antiocoagulant therapy, the correlation coefficients between the doses of Sintrom and the prothrombin value of the nex day were calculated for each patient and each week separately. An analysis of variance did not show any statistically significant difference between the correlation coefficients of the weeks with and without Ludiomil therapy, i.e. there is no change in the efficacy of the anticoagulant therapy. During the Ludiomil therapy the control of the anticoagulant therapy was slightly better, i.e. the fluctuations of the prothrombin values less, but statistically these differences were not significant. The plasma levels of Ludiomil in these patients were similar to thse found previously in both depressed and healthy volunteers.

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A double-blind crossover trial between diclofenac sodium and placebo was carried out in 32 hospitalized patients who were thought to be stabilized on concurrent anticoagulant therapy with acenocoumarol. The object of the trial was to investigate any possible interaction between diclofenac and anticoagulant by monitoring prothrombin times daily through the four week period. No statistically significant difference between placebo and diclofenac could be shown and some problems of accurately monitoring prothrombin times are discussed.

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