Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bepridil hydrochloride is a unique calcium channel-blocking drug with anti-ischemic and type 1 antiarrhythmic properties. With a half-life of more than 40 hours, once-daily therapy is possible. Twenty-four patients (22 men, 2 women), mean age 58 years (range 43 to 72), with stable exertional angina were assigned to therapy with bepridil and nadolol in a randomized, double-blind, crossover trial. Antianginal efficacy was assessed by a diary of angina frequency and nitroglycerin consumption as well as by treadmill exercise testing. The effect of therapy on ventricular function was assessed by symptom-limited equilibrium gated exercise radionuclide angiography. During therapy with both nadolol and bepridil, the number of episodes of angina per week was significantly reduced and nitroglycerin consumption decreased compared with baseline evaluation. Exercise duration was prolonged by both therapies (baseline 281 +/- 122 seconds, nadolol 377 +/- 96 seconds, bepridil 400 +/- 109 seconds; p less than 0.005 for nadolol and bepridil vs baseline). Time to the onset of angina was similarly prolonged, 50% by nadolol and 65% by bepridil (p less than 0.005). Bepridil had no effect on PR and QRS durations, although QTc was significantly prolonged (baseline 0.43 +/- 0.03, nadolol 0.42 +/- 0.03, bepridil 0.45 +/- 0.04; p less than 0.005 for bepridil vs baseline and nadolol). By radionuclide angiography, neither nadolol nor bepridil had an adverse effect on left ventricular function at rest or during exercise. Bepridil therefore provides effective therapy for angina without adverse effects on left ventricular function, comparable to the effects of beta blockade with nadolol.
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PMID:Comparison of bepridil with nadolol for angina pectoris. 329 24

Bepridil hydrochloride differs from the other calcium antagonists in structure as well as in several clinical pharmacokinetic characteristics. The drug is completely absorbed from the gastrointestinal tract, but first-pass extraction reduces oral bioavailability to approximately 60%. After single-dose administration, the elimination half-life of bepridil averages 33 +/- 15 hours. However, upon multiple dosing, a half-life of 42 +/- 12 hours is found. As with verapamil and diltiazem, bepridil clearance is decreased after multiple dosing. Bepridil is completely metabolized, presumably by hepatic oxidative processes. A total of 17 metabolites have been identified, but the contribution of any of these metabolites to observed clinical response is currently unclear. The free fraction of bepridil in plasma is low, averaging only 0.23%. Despite this high protein binding, in vitro studies indicate that the potential for drug-to-drug interactions based on displacement of bepridil from its binding sites is low. Bepridil follows a linear dose/plasma concentration relation after single and multiple doses of the drug in both healthy volunteers and patients with angina. However, mean steady-state plasma bepridil concentrations are higher in patients, indicating a greater average decreased clearance. Food does not interfere with bepridil absorption. At this time, no significant pharmacokinetic interactions between bepridil and digoxin have been detected.
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PMID:Pharmacokinetics and metabolism of bepridil. 387 57

The binding of the calcium-channel blocking agent, bepridil HCl (Vascor), to plasma proteins was investigated using radiolabeled bepridil and equilibrium dialysis. Greater than 99.7% of added bepridil-14C was found to freshly collected human plasma. The binding was characterized by a saturable high-affinity site (KD = 32 ng/mL = 87 nM) on alpha1-acid glycoprotein (AAG) or on an AAG-human serum albumin complex and lower affinity binding sites on albumin and other plasma macromolecules. Bepridil that is not bound to plasma proteins is extensively distributed into erythrocytes as evidenced by a red blood cell to free drug distribution coefficient of 71 +/- 7. Despite this high value, the blood to plasma ratio of bepridil averaged only 0.67 in humans, indicating that most of the circulating drug is bound to plasma proteins. Bepridil protein binding was not affected by additions of nonesterified fatty acids. Free fractions of bepridil were enhanced by addition of verapamil, nifedipine, diltiazem, disopyramide, and warfarin but only at concentrations above those achieved clinically. Bepridil was also displaced by the plasticizer, tris-(2-butoxyethyl)phosphate. Plasma obtained from a small number of angina patients prior to bepridil administration showed no differences in ability to bind bepridil compared with plasma obtained from healthy subjects.
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PMID:Plasma protein binding of bepridil. 387 35

A total of 178 patients participated in a 14-week, multicenter, double-blind, parallel study to evaluate the comparative efficacy and safety of single daily doses of 200, 300 and 400 mg of bepridil hydrochloride and placebo in the treatment of patients with chronic stable angina pectoris. The results showed that weekly angina attacks and nitroglycerin consumption were significantly reduced from baseline levels with all doses of bepridil (p less than 0.01), and the reductions were consistently greater than those in the placebo group. For the 400-mg dose the reductions in angina attacks and nitroglycerin consumption were significantly greater (p less than or equal to 0.05) than those in the placebo group at all but 1 evaluation point. Exercise tolerance improved significantly during bepridil administration (p less than or equal to 0.05), and a significant linear dose response was noted for total exercise time, total work and time to onset of angina. In addition, bepridil was significantly superior to placebo for these parameters at doses of 300 (p less than or equal to 0.05) and 400 mg (p less than or equal to 0.01). There were small reductions in heart rate (mean 3.7 beats/min) and prolongation of QT and QTc intervals (approximately 30 to 40 milliseconds) associated with bepridil treatment. Bepridil was well tolerated by patients in this study. When adverse effects occurred, they most frequently involved the gastrointestinal and central nervous systems. Of the patients receiving bepridil, 6% discontinued therapy because of adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative efficacy of 200, 300 and 400 mg of bepridil for chronic stable angina pectoris. 391 56

To evaluate whether bepridil once a day provides effective antianginal therapy during extended use, a placebo-controlled withdrawal study was conducted in 33 patients with chronic stable angina. Each patient studied had previously had a favorable response to short-term administration of bepridil and had been taking the drug once daily for greater than or equal to 9 months of continuous use. Patients were then randomly assigned to receive either continued bepridil or a placebo substitution once daily during a 4-week, double-blind, parallel-group comparison. Dosage for the bepridil group was constantly maintained for each patient at a level observed to be clinically effective. The study consisted of a comparison of angina frequency and nitroglycerin tablet consumption obtained from patient diaries and results from maximal-graded multistage treadmill tests. Patients randomized to continue receiving bepridil remained stable in terms of angina frequency and exercise performance. Discontinuation of long-term bepridil significantly increased angina frequency and nitroglycerin tablet consumption and reduced exercise capacity. Four patients (24%), all receiving placebo treatment, had increases in angina frequency and had the study terminated. Bepridil was reinstituted in these patients with resolution of symptoms and no untoward effects. The results of this placebo-controlled, double-blind, randomized study confirm that bepridil continues to provide antianginal benefit during long-term administration.
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PMID:Long-term efficacy of bepridil in patients with chronic stable angina pectoris: results of a multicenter, placebo-controlled study of extended bepridil use. 391 57

Bepridil, a new anti-anginal drug, was given in a daily dosage of 400 to 600 mg to twenty patients with unstable angina pectoris. The trial was designed to evaluate the effectiveness of bepridil in this indication and to determine the optimal dosage. A positive response evidenced by the arrest of progression towards infarction was recorded in 17 patients. Tolerance was satisfactory in 19 cases: in one diabetic patient under insulin symptoms of hypoglycemia resolved once insulin was discontinued. With the dosages used the effectiveness of bepridil in unstable angina pectoris is similar to that recorded in effort angina with 300 mg per day.
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PMID:[A clinical trial of the effectiveness and tolerance of bepridil in unstable angina pectoris]. 629 63

Bepridil, a new calcium-channel blocking agent with an extended plasma elimination half-life of greater than 50 hours, was compared to placebo in 77 patients with confirmed coronary artery disease and chronic stable angina pectoris. The effects of bepridil were compared with those of placebo on angina frequency, nitroglycerin tablet use, the resting ECG and hemodynamics at rest and maximal exercise using a study design comprising 5 sequential 2-week single-blind treatment phases. After 2 weeks of placebo (phase 1), bepridil was given for 3 phases (2, 3 and 4) at total daily dosages of 200, 300 and 400 mg, respectively; the study was completed after a final reintroduction of placebo (phase 5). Within each phase once- and twice-daily regimens of bepridil were randomly compared. Bepridil (300 mg/day) reduced anginal frequency 68%, from 8.5 +/- 1.1 (standard error of the mean) to 2.7 +/- 0.7 attacks/week and nitroglycerin tablet use 76% (p less than 0.001). Bepridil improved exercise duration 26%, from 6.9 +/- 0.4 to 8.7 +/- 0.5 minutes (p less than 0.001) and exercise work 52%, from 2.7 +/- 0.3 to 4.1 +/- 0.4 kpm X 10(-3) (p less than 0.001) on a standardized treadmill protocol. Resting and peak exercise heart rate and blood pressure were unaffected by bepridil. The antianginal effects were similar with either once- or twice-daily treatment schedules. Minor side effects of nausea, epigastric discomfort and tremor were infrequent and there were no major side effects. The results of this large but preliminary, single-blind and short-term study suggest that bepridil is an effective and well tolerated antianginal agent when administered once daily.
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PMID:Bepridil for chronic stable angina pectoris: results of a prospective multicenter, placebo-controlled, dose-ranging study in 77 patients. 636 86

Bepridil, a calcium antagonist with a half-life of approximately 42 hours, was compared with placebo in a double-blind, randomized, crossover trial. Thirteen men (average age 62 years) with exercise-related angina pectoris and a positive exercise test (modified Bruce protocol) were studied. In the group as a whole, bepridil (400 mg once a day) caused an increased total exercise time (2.6 +/- 1.8 minutes, mean +/- standard deviation), time to onset of angina (3.3 +/- 1.6 minutes), time to 1 mm of ST-segment depression (2.2 +/- 2.3 minutes), time to 2 mm of ST-segment depression (2.4 +/- 1.4 minutes) and total work load achieved (1.8 +/- 1.4 kpm) compared with the preceding placebo phase (all p less than 0.05). Frequency of angina and nitroglycerin consumption were low and did not change significantly during bepridil therapy. Comparison of the 3 placebo periods (run-in, double-blind and washout) did not reveal a change in any measurement except time to onset of angina, suggesting no training effect or change in patient status. Adverse effects were common in patients taking both placebo and bepridil, but only 2 patients had adverse effects (dizziness) with bepridil that necessitated discontinuation of therapy. Similarity of the double product (systolic blood pressure X heart rate) at the end of exercise suggests a decrease in myocardial oxygen demand as the primary mode of action. This study suggests that bepridil is a promising agent for the treatment of exercise-induced myocardial ischemia.
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PMID:Effects of bepridil on exercise tolerance in chronic stable angina: a double-blind, randomized, placebo-controlled, crossover trial. 636 14

Patients with coronary artery disease and angina pectoris have abnormalities of left ventricular (LV) diastolic performance. These abnormalities, which exist when the patients are at rest and not experiencing angina, are presumably secondary to abnormalities of intracellular calcium metabolism. Twenty-three patients with chronic exertional angina pectoris participated in a placebo-controlled, randomized, cross-over trial of bepridil hydrochloride. Angina frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were assessed, and each patient underwent first-pass radionuclide cineangiography while receiving placebo or bepridil to assess LV performance. Bepridil decreased angina frequency from 8.5 +/- 0.6 to 4.4 +/- 1.5 episodes per week (p < 0.01) and NTG consumption from 7.2 +/- 2.4 to 3.6 +/- 1.5 tablets per week (p < 0.01). Total treadmill exercise time, time to onset of angina, and time to 1-mm ST segment depression increased significantly during bepridil therapy. Cardiac output (CO), stroke volume (SV), and ejection fraction (EF) increased at rest and during peak upright bicycle exercise. Peak ejection rate and peak filling rate increased, and time to peak ejection rate and time to peak filling rate decreased at rest and at peak exercise during bepridil therapy. In addition, early diastolic filling fraction increased and atrial filling volume decreased during bepridil treatment. Bepridil is effective as monotherapy for treatment of patients with exertional angina; its use is associated with increased exercise capacity and decreased angina frequency and NTG consumption as well as improved LV systolic and diastolic performance at rest and during peak exercise.
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PMID:Bepridil improves left ventricular performance in patients with angina pectoris. 750 41

Bepridil has been used only rarely in unstable angina since its long half-life could imply a delayed action. A loading dose could deal with this disadvantage. In order to confirm this hypothesis, a randomised trial was undertaken involving a 5 day comparison of bepridil at the dose of 300 mg/day after a loading dose (900 mg on D1, 500 mg on D2 and D3) with diltiazem 360 mg/day in 277 patients: 210 men and 67 women, with a mean age of 62.1 +/- 9.5, suffering from unstable angina confirmed by an ECG during symptomatic events showing reversible ST depression. A continuous 72 hour ECG record was obtained in 82 patients. Because of 69 inclusion errors, only 208 patients provided evaluable data (110 with bepridil and 98 with diltiazem), including 55 with continuous ECGs. Mortality (4.5% bepridil v. 3.1% diltiazem) and premature treatment terminations for therapeutic inefficacy (4.5% bepridil v. 7.1% diltiazem), myocardial infarction (3.6% bepridil v. 3% diltiazem), adverse events (3.6% bepridil v. 3% diltiazem) or at the patient's request (0.9% bepridil) were similar between the 2 groups. Efficacy regarding angina was similar, with 18.2% recurrences with bepridil and 21.4% with diltiazem during the first 72 hours, persisting without any difference beyond 72 hours. Resulting treatment adjustments concerning nitrates were identical in the 2 groups. Among the 55 patients with an evaluable continuous ECG (27 bepridil and 28 diltiazem, NS), 18 had recurrent ischemic episodes (9 bepridil and 9 diltiazem), 72.2% of which were clinically silent. Their total number, total duration and maximum amplitude of ST depression were similar in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative study of the efficacy and tolerability of bepridil and diltiazem in unstable angina. 277 patients]. 817 82


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