Antihypertensive effect of amlodipine and lack of interference with cyclosporine metabolism in renal transplant recipients.

The catabolism of various calcium channel blockers through cytochrome P-450 is heterogeneous and may be modified by concomitant use of cyclosporin A. In an open study we investigated the antihypertensive effect and clinical tolerance of the dihydropyridine amlodipine and its effects on cyclosporine kinetics in stable hypertensive renal transplant recipients not taking corticosteroids. Ten adult hypertensive patients grafted for 21.4 +/- 8.9 months and well stabilized with normal renal function were included in the study. Renal artery stenosis was ruled out by normal Doppler echography. After 2 weeks of placebo, amlodipine was started at a daily dose of 5 mg. The dose was then adjusted to 10 mg if necessary. Blood and urine chemistries and whole-blood cyclosporine trough levels were measured weekly. Cyclosporine kinetics were determined on a hourly basis before amlodipine administration and after 4 weeks of treatment. Normal blood pressure was obtained with the use of 5 mg/d amlodipine in 7 patients and 10 mg/d in 3, diastolic blood pressure decreasing from 98.7 +/- 3.8 to 81.3 +/- 9.1 mm Hg (P = .0007). Heart rate slightly increased by 10% (P < .02). The drug was well tolerated, and only minor ankle edema was found in 3 patients. Cyclosporine doses were not modified and cyclosporine levels remained unchanged throughout the study. Cyclosporine kinetic parameters were not significantly different at the beginning and end of the study. Bioequivalence was demonstrated indicating that cyclosporine biotransformation was not altered by the concomitant administration of amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Compliance and antihypertensive efficacy of amlodipine compared with nifedipine slow-release.

Poor compliance is a principal cause of treatment failure in hypertensive patients. Once-daily dosing improves compliance, but 24-h antihypertensive activity should be provided. The compliance, efficacy, and safety of amlodipine and nifedipine slow-release (SR) were compared in patients with mild-to-moderate essential hypertension recruited among 24 centers in France. After a 2-week washout period, 103 patients were randomized to 12 weeks of 5 to 10 amlodipine mg once daily (n = 55) or 20 mg nifedipine SR twice daily (n = 48). Compliance was calculated by electronic drug monitoring. Efficacy was measured by ambulatory and casual BP recordings. Patients receiving amlodipine demonstrated better compliance than patients receiving nifedipine SR with respect to compliance index (the total number of doses taken divided by the total number of doses prescribed, expressed as a percentage; 98.3% v 87%; P < .0001), days on which the correct number of doses were taken (92.5% v 74.8%; P < .0001), and prescribed doses taken on schedule (88.7% v 71.6%; P < .0001). Absolute and relative therapeutic coverage were higher in patients receiving amlodipine than nifedipine SR (P < .0001). Mean SBP and DBP decreased equally in both groups, although amlodipine offered better BP control compared with nifedipine SR at specific times of day. Fewer patients had high nocturnal SBP with amlodipine (39.3%) than nifedipine SR (71.4%; P = .042). Adverse events and treatment withdrawals occurred less frequently in amlodipine-treated patients than in nifedipine SR-treated patients. Amlodipine (5 to 10 mg) once daily provides improved compliance, better 24-h BP control, and fewer adverse events than 20 mg nifedipine SR twice daily in patients with mild-to-moderate hypertension.

Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France.

In a double-blind study in a primary-care setting in France, outpatients fulfilling DSM IV criteria for a major depressive episode were randomised to receive sertraline (50 to 150 mg/day; n = 122) or fluoxetine (20 to 60 mg/day; n = 120). Assessments, including clinical evaluation [Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI)] and quality of life [Functional Status Questionnaire (FSQ)], were made at study entry and after 4 and 6 months of treatment. Use of medical services, absences from work and productivity losses were recorded for calculation of direct and indirect costs from both the overall societal perspective and in terms of sickness insurance. In total, 231 patients (116 receiving sertraline, 115 receiving fluoxetine) were included in an intention-to-treat analysis assessed up to the last visit. Statistically significant clinical and quality-of-life improvements from baseline were observed in both treatment groups, with no between-group differences. Utilisation of medical resources was higher in fluoxetine-treated patients, with significantly more consultations with specialists. The 2 treatment groups were similar in terms of number of hospitalisations and duration of stay, whether related to depression or not. There were no significant differences between groups for work or productivity losses. Cost comparisons favoured sertraline treatment from both the societal (FF7780 vs FF8706) and sickness insurance (FF2936 vs FF3224) viewpoints, with cost differentials of FF926 and FF288, respectively. From the societal perspective, the total cost per patient over the 6-month course of the trial, irrespective of the study treatment given, was FF8241, and the corresponding sickness insurance cost was FF3079. At the time of the study, FF1 = $US0.1993.

[Bepridil and bundle of His block. Apropos of a case]. / Bépridil et bloc intrahisien. A propos d'un cas.

The first case of atrioventricular block located in His bundle observed during oral treatment with bepridil is reported; the block subsided when the drug was discontinued and reappeared when it was reintroduced. Electrophysiological studies performed with bepridil have shown that, as could be foreseen from its beneficial or undesirable effects, this calcium antagonist has some properties of Vaughan Williams' class I antiarrhythmic agents and alters subnodal conduction. Clinical studies indicate that in therapeutic doses this alteration has little or no significance, but it may reach clinical expression when latent of patient pre-existing disorders of conduction within or below His bundle are present.

Could inspiratory apnea disturb left ventricular volume assessment by contrast angiography?

To assess the influence of postinspiratory apnea on the measurement of the left ventricular volumes, contrast ventriculography was performed on 19 patients during spontaneous breathing and then in postinspiratory apnea. Data obtained were similar for end diastolic volumes (81 +/- 29 ml/m2 vs. 83 +/- 25; NS), end systolic volumes (35 +/- 20 ml/m2 vs. 34 +/- 19; NS), systolic index (46 +/- 13 ml/m2 vs. 49 +/- 12; NS), and ejection fraction (0.57 +/- 0.11 vs. 0.59 +/- 0.12; NS). Postinspiratory apnea suppressed the overlapping of the left ventricle with abdominal viscera in 15 of 17 patients. Diaphragmatic immobility permitted the assessment of regional left ventricular function in all 19 patients. However, pressures recorded in inspiratory apnea can no longer be compared to a transmural pressure, and, to assess ventricular compliance, intrapleural pressure must be measured simultaneously. We conclude that left ventricular volume assessment by contrast ventriculography is not disturbed by inspiratory apnea. This maneuver improves the quality of the images and allows a better evaluation of left ventricular segmental function. Spontaneous breathing can be recommended to simplify left ventricular compliance study.

Economic analysis of antibiotic regimens used in the treatment pharyngitis: a prospective comparison of azithromycin versus roxithromycin.

The economic impacts in terms of cost and effectiveness (speed of resolution of symptoms) of 3- and 5-day courses of azithromycin and a 10-day course of roxithromycin were compared in a randomized, open study in patients with symptoms suggestive of beta-haemolytic streptococcal pharyngitis. Direct medical costs and absence from work were recorded and symptom scores and compliance were used to assess the effectiveness of therapies. Although no differences between treatment groups in terms of overall clinical response rates were detected 2 and 4 weeks after the start of treatment, more rapid resolution of symptoms was achieved with 3- and 5-day courses of azithromycin than with a 10-day course of roxithromycin. There was also a significant reduction in the time absent from work in the azithromycin treatment groups. The total costs of care over the 4-week evaluation period were lower for the 3- and 5-day azithromycin courses (US$193.60 and US$195.30 respectively) than for roxithromycin (US$202.10). The major cost components were absence from work (58.6%), visits to the physician (15.3%) and utilization of antibiotics (14.9%). Compliance was significantly better (P < 0.01) in patients prescribed azithromycin for 3 and 5 days (58.0% and 42.9% respectively) than in those who received roxithromycin (20.3%) and a significantly longer symptom-free period (P < 0.01) was reported in azithromycin- compared with roxithromycin-treated patients. These findings support the hypothesis that a 3- or 5-day course of azithromycin is as effective as a 10 day course of roxithromycin in the treatment of patients with pharyngitis and is associated with lower costs. Furthermore, azithromycin is associated with faster resolution of symptoms and improved patient compliance.

Acute hemodynamic effects of amlodipine 15 days after a myocardial infarction in normotensive patients treated with atenolol.

The acute hemodynamic effects of 20 mg iv amlodipine were evaluated in a placebo-controlled study in 16 normotensive patients 15 +/- 1 days after an acute myocardial infarction by covariance analysis. Atenolol was given orally for at least 1 week before the study to maintain the heart rate between 50 and 60 beats/min. All patients were given two doses of 10 mg of amlodipine, or 10 ml of a placebo twice, in i.v. infusion lasting 2 minutes each. Hemodynamic data were collected during the control period and 15 minutes after each of the two amlodipine or placebo infusions. At the time of the last measurements, 15 minutes after the second amlodipine or placebo infusion, the plasma amlodipine level was 31 +/- 16 micrograms/l and the plasma atenolol level was 773 +/- 564 mu/l in the amlodipine group versus 795 +/- 916 micrograms/l in the placebo group. There were no chronotropic, dromotropic, or inotropic effects. The main hemodynamic effect was a fall in systemic vascular resistance (1548 +/- 591 dynes.sec.cm-5 to 1176 +/- 526 dynes.sec.cm-5, p = 0.045) with decreases in aortic pressure and in the left ventricular stroke work index. The left ventricular ejection fraction was 51 +/- 12% in the placebo group and 56 +/- 15% in the amlodipine group (ns) during the control period, and did not change after infusion of placebo or amlodipine. Left ventricular compliance seemed to be enhanced by amlodipine, because the end-diastolic left ventricular volume index rose from 82 +/- 11 ml/m2 to 87 +/- 11 ml/m2 (p = 0.026) 15 minutes after the beginning of the second infusion of 10 mg of amlodipine, without any change in end-diastolic left ventricular pressure. Intravenous infusion of 20 mg of amlodipine is well tolerated 15 days after acute myocardial infarction in normotensive patients without deeply depressed left ventricular systolic function and chronically treated with atenolol. The main hemodynamic effects observed are potentially useful for such patients.