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D Piovan

Publications and source records attributed to D Piovan.

51 records · Page 3Linked to original sources

Plasma levels and urinary excretion of verapamil, norverapamil, N-dealkylverapamil (D617), N-dealkylnorverapamil (D620) following oral administration of a slow-release preparation.

The kinetics of verapamil and of its N-dealkylated metabolites (norverapamil, D617, D620) were studied in six cardiac patients with normal cardiac indexes after 120 mg oral administration of the drug both as conventional preparation and as slow-release preparation. Following a dose of the slow-release preparation, the drug concentration curves were smoother and the mean bioavailability was lower in comparison with the conventional preparation. A patient taking inducing agents (phenobarbital and phenytoin) exhibited a strikingly low bioavailability. Following administration of the conventional preparation, the mean plasma half-lives of verapamil, norverapamil, D617 and D620 were 4.4, 6.6, 8.5, and 15.8 h respectively and the drug concentrations showed a triexponential decay. Urinary excretion data indicate that a saturation phenomenon may occur at level of renal tubular transport and that a competition may be suspected between D620 and the other compounds. It is concluded that various mechanisms, i.e. changes in hepatic and renal clearances, occurrence of a deep compartment, and the properties of the pharmaceutical preparation may affect verapamil kinetics during long-term treatment.

Adult↗

Use of oral verapamil in long-term treatment of neonatal, paroxysmal supraventricular tachycardia. A pharmacokinetic study.

Efficacy and pharmacokinetics of verapamil were studied in two neonates affected by supraventricular paroxysmal tachycardia, under maintenance treatment with the drug. Verapamil proved to be fully effective in suppressing arrhythmic episodes at the daily doses of 1.5 mg/kg four times a day in case 1 and of 2 mg/kg in case 2. The results of plasma half-life of the drug, calculated in a dose interval, were 3.14 hr and 2.10 hr, respectively. In patient 2, doses less than 0.95 mg/kg four times a day did not produce detectable drug plasma levels, while a further stepwise increase of dose up to 2 mg/kg four times a day produced a steep rise in trough concentration. So, in view of this dose-concentration relationship, caution is recommended in adjusting verapamil oral dosage.

Administration, Oral↗

[Pharmacological and clinical research on the interaction of digitalis and amiodarone in heart disease patients with varying degrees of cardiac insufficiency].

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

Adult↗

A report on the positive inotropic action of amrinone.

The inotropic action of amrinone was evaluated on isolated guinea-pig atria and on specimens of human atrial myocardium. The drug elicited a positive inotropic response in both the tissues. On spontaneously beating guinea-pig atria the influence on contractility was higher than on the rate. The magnitude of the response was influenced by temperature. Propranolol or phentolamine did not affect the positive inotropic action of amrinone. The efficacy of amrinone was higher than ouabain, in normal as well as in low extracellular calcium. Amrinone showed a positive inotropic action also at high extracellular potassium. The positive staircase was not reversed by amrinone, which had a higher positive inotropic effect at higher frequency of driving; the drug did not significantly delay the decline of contractile force in zero calcium. It is possible that the inotropic effect of amrinone in mainly due to an effect on influx of calcium into the cells.

Aminopyridines↗

Influence of age and gender on the in vitro serum protein binding of flecainide.

The in vitro protein binding of flecainide was studied by equilibrium dialysis in relation to serum concentrations of albumin and alpha 1-acid glycoprotein (AAG) in 22 healthy subjects of both sexes aged between 23 and 89 years. In the range of flecainide concentrations tested, protein binding of flecainide was not saturable and the percent value of the unbound fraction ranged between 0.48 and 0.68, mean value (SD) = 0.59 (+/- 0.06), without any significant difference between males and females or between young and old subjects. The flecainide unbound fraction was significantly correlated with serum albumin concentrations but not with total serum proteins or AAG concentrations.

Adult↗

Evaluation of the regional responsivity to ryanodine of human myocardium from patients with idiopathic dilated cardiomyopathy and secondary cardiomyopathies.

The aim of the study was to compare the contractile response to ryanodine of human heart preparations taken from right and left ventricles of patients affected by idiopathic (IDCM) and secondary (SCM) end-stage dilated cardiomyopathies. Right and left ventricle myocardial strips were obtained from hearts of patients undergoing orthotopic heart transplantation and suspended in an oxygenated bath (T = 35 degrees C; stimulation frequency = 0.5 Hz). After an equilibration period, a cumulative dose-response curve for contractility (peak tension) was obtained with ryanodine (0.5, 1, 2, 4, 8, 16, 32, 64 microM). Basal contractility was not significantly different between right and left ventricles or between IDCM and SCM preparations. Ryanodine reduced peak myocardial tension but failed to completely suppress it, even at concentrations which achieved maximum effect. Ryanodine effect still persisted after a 45'-60' washout. The concentration-effect curves from IDCM right ventricle, IDCM left ventricle, SCM right ventricle and SCM left ventricle were compared: IDCM left ventricle was less sensitive to ryanodine than IDCM right ventricle and SCM left ventricle, while no difference was detectable between SCM left ventricle and SCM right ventricle. Thus, the overall sensitivity ranking was: IDCM left ventricle < IDCM right ventricle = SCM right ventricle = SCM left ventricle. IDCM left ventricle showed, in addition, a biphasic response with a shift from negative to positive inotropic effect at concentrations higher than approximately 10 microM. These findings indicate that the cardio-depressant effect of ryanodine, a drug which interferes with intracellular Ca release from the sarcoplasmic reticulum, differs quantitatively and qualitatively in IDCM left ventricle from both IDCM right ventricle and SCM left ventricle. This suggests that some specific alteration in the intracellular Ca signalling in IDCM exists and, from a methodological point of view, stresses the need for a "bi-ventricular" approach to studying biochemical and functional abnormalities of advanced congestive heart failure.

Adult↗

Long-term persistence of antianginal effect of oral verapamil in chronic stable angina.

The long-term antianginal effect of orally administered verapamil over 1 year of continuous treatment was assessed in 11 patients with effort-induced angina. In the short-term phase of the study, patients were given, in random order, placebo and verapamil (360 mg/day). The tolerated work load during a bicycle exercise test was 531.8 +/- 123.0 kg/min on placebo and 763.6 +/- 124.7 kg/min on verapamil (p less than 0.001). Subsequently all patients entered a long-term study of 1-year continuous treatment with 120 mg t.i.d. verapamil. The tolerated work load at 8-week (736.4 +/- 105.1 kg/min) and 1-year (804.6 +/- 101.1 kg/min) tests did not significantly differ from the results in the short-term study. The average verapamil plasma level was 138.5 +/- 90.6 ng/ml before and 357.8 +/- 199.2 ng/ml 90 min after drug administration; the average norverapamil plasma levels were, respectively, 248.0 +/- 84.4 and 368.0 +/- 135.9 ng/ml. There was no correlation between verapamil or norverapamil plasma concentrations and the antianginal effect. No patient developed signs of heart failure during the treatment. Two patients had mild constipation. The average P-R interval was slightly, although significantly (p less than 0.01) prolonged, but no patient developed first-degree atrioventricular block. We conclude that verapamil proves an effective and safe drug in the treatment of effort-induced angina; the beneficial effects of the short-term treatment are sustained during 1 year of continuous treatment.

Administration, Oral↗