ABSTRACT
The present study was performed to see if the combined treatment with nifedipine and dilazep offers any advantage over monotherapy with nifedipine alone in angina of effort. Thirty-three patients out of 40 with classical stable angina of effort completed this double-blind, randomized, parallel design comparative clinical trial. Both nifedipine alone (15-60 mg) and in combination with dilazep (50 mg) three times a day produced a significant reduction in angina attacks, consumption of nitroglycerin tablets and increased exercise tolerance. There was, however, no difference in the reduction in these parameters between the two groups. There was no significant reduction in blood pressure both systolic as well as diastolic and rate pressure product both when nifedipine was given alone and when it was given in combination with dilazep. Laboratory data did not reveal any dysfunction of liver, kidney and hemopoietic system. The results obtained show that there was no beneficial effect of adding dilazep to nifedipine therapy in the treatment of angina pectoris.
Subject(s)
Angina Pectoris/drug therapy , Dilazep/therapeutic use , Nifedipine/therapeutic use , Dilazep/administration & dosage , Dilazep/adverse effects , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Nifedipine/administration & dosage , Nifedipine/adverse effectsABSTRACT
The present study was performed to see if the combined treatment with propranolol and dilazep offers any advantage over monotherapy with propranolol alone in angina of effort. Thirty-four patients out of 40 with classical stable angina of effort completed this double-blind, randomized, parallel design comparative clinical trial. Both propranolol alone (20-80 mg) and in combination with dilazep (50 mg) three times a day produced a significant reduction in anginal attacks, consumption of nitroglycerin tablets and increased exercise tolerance. Propranolol in combination with dilazep produced more reduction in these parameters as compared to when it was given alone. However, this difference was not significant. The combination of the two drugs produced a significant reduction in supine systolic blood pressure and in rate-pressure product. Laboratory data did not reveal any dysfunction of liver, kidneys and hemopoietic system. The results obtained support the anticipated additional benefit from combined therapy with propranolol and dilazep in terms of some increase in efficacy.
Subject(s)
Angina Pectoris/drug therapy , Azepines/administration & dosage , Dilazep/administration & dosage , Propranolol/therapeutic use , Clinical Trials as Topic , Coronary Circulation/drug effects , Dilazep/adverse effects , Drug Therapy, Combination , Exercise Test , Female , Humans , Male , Propranolol/administration & dosage , Propranolol/adverse effectsABSTRACT
The oral dose metabolism of dilazep dihydrochloride [tetrahydro-1H-1,4-diazepine-1,4(5H)-dipropanol 3,4,5-trimethoxybenzoate] was examined in six hypertensive patients receiving a single oral dose of 600 mg of dilazep (3-3.8 mg/kg BW). Blood was collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 h after administration of the dose and urine was collected for three time intervals of 0-4 h, 4-10 h, and 10-24 h. Dilazep concentrations in blood and urine were determined by high-performance liquid chromatography. Dilazep decayed monoexponentially with a mean elimination rate constant of 0.27 +/- 0.13 h-1 and a mean half-life of 3.04 +/- 1.34 h. The mean tmax of absorption was 1.40 +/- 0.82 h. With maximally tolerated chronic doses, the steady-state concentration measured at 1 week was 25.6 ng/mL in a patient receiving 300 mg daily (100 mg TID) for 3 weeks, and dilazep concentration increased with the dose in others for up to a 600-mg dose daily. Dilazep did not produce any significant changes in heart rate and blood pressure after a single oral dose or during chronic dosing. There was no correlation between blood dilazep levels and the changes in heart rate and blood pressure. In three additional patients, oral dilazep dihydrochloride titrated gradually to maximally tolerated doses (900 mg daily) failed to produce significant effects on biochemical and neurohumoral measurements, and hemodynamic parameters as well as ventricular functional indices measured by radionucleide methods. Oral dilazep administration in maximally tolerated doses is devoid of effects on blood pressure and cardiac hemodynamic function.
