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Biomedical subjects

P Jaillon

Publications and source records attributed to P Jaillon.

At least 127 records · Page 7Linked to original sources
PubMed1985

Suppression of arrhythmias within hours after a single oral dose of amiodarone and relation to plasma and myocardial concentrations.

In 65 patients a single oral dose of amiodarone (30 mg/kg) produced an antiarrhythmic effect on supraventricular or ventricular arrhythmias within 3 to 8 hours and lasted for 17 to 19 hours. On the second day a 15-mg/kg dose reproduced this effect within 3 to 9 hours. Plasma concentration of amiodarone increased to a maximum (2.2 +/- 1.7 mg/liter) mean +/- standard deviation) at 6 +/- 3.5 hours and plasma levels of N-desethylamiodarone (NDA) rose to 0.2 +/- 0.08 mg/liter at 12 +/- 6.4 hours. Sixty-one other patients were given a single 30-mg/kg dose 7 hours to 4 days before open heart surgery. Biopsies of the right atrial and left ventricular walls were taken during surgery. Myocardial concentration of amiodarone was maximal in the atrium after 7 hours (13 +/- 8 mg/kg) and in the ventricle after 24 hours (17 +/- 11 mg/kg). NDA myocardial concentration increased progressively until 24 hours and then remained stable over 4 days (1.5 mg/kg). The amiodarone myocardial to plasma concentration ratio was similar in the atrium and in the ventricle and averaged 22 and 10 for amiodarone and NDA, respectively. A significant relation existed between amiodarone concentration and the effect on ventricular premature complexes (r = 0.74, p less than 0.001) and between amiodarone plasma concentration and the effect on the atrioventricular conduction (r = 0.58, p less than 0.001). The plasma concentration of amiodarone corresponding to a 60% decrease in arrhythmias averaged 1.5 to 2 mg/liter.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Long-term efficacy and safety of oral encainide in the treatment of chronic ventricular ectopic activity: relationship to plasma concentrations--a French multicenter trial.

To establish long-term efficacy and safety of encainide, 48 patients with chronic premature ventricular contractions (PVCs) underwent 6 months of therapy with encainide. Twenty-four-hour ambulatory ECGs were obtained at baseline for each daily dosage of 75 mg, 150 mg, and 225 mg of encainide during the in-hospital titration period and at the end of the first and sixth months during the follow-up period. There was a significant reduction in the median hourly total PVC rates from 480.6 at baseline to 2.0 at the end of the titration period with the highest dosage and to 22.1 at the last visit of the chronic dosing period. Nearly total suppression of PVCs was observed in 56% of patients at the end of the titration period and in 30% at the end of the 6-month follow-up period. The most common side effects were vertigo, vision disturbance, and headache. PR, QRS, and QTc intervals showed consistent significant increases from baseline during the various encainide trial periods. Encainide may have worsened ventricular arrhythmia in four patients who received more than 200 mg of encainide daily. Plasma concentrations of encainide and encainide metabolites showed wide interpatient variation, and no relationship was found between antiarrhythmic efficacy and plasma levels of encainide, O-demethyl-encainide, or 3-methoxy-O-demethyl-encainide.

Adolescent↗
PubMed1985

Intrinsic hepatic clearance and Child-Turcotte classification for assessment of liver function in cirrhosis.

Child-Turcotte classification (CTC) is an empirical but widely accepted approach for assessment of severity of cirrhosis. However, it is not known to what extent CTC reflects accurately the degree of impairment of hepatic function. In this study we compared CTC, standard liver tests and intrinsic hepatic clearance (IHC) of indocyanine green as means of assessing hepatic function in 63 cirrhotic patients. As compared to 10 control patients, IHC was significantly decreased in the cirrhotic group: (mean +/- SD) 0.270 +/- 0.141 l/min vs 1.227 +/- 0.312 l/min (P less than 0.001). Serum bilirubin (SB), prothrombin time (PT) and serum albumin were significantly correlated with the degree of IHC impairment while alkaline phosphatase, ALAT and clinical criteria of CTC were not. Multivariate analysis showed that SB and PT were the only 2 variables that significantly explained the impairment of IHC. The model which best explained IHC impairment was Z = 21.77 + 4.78 PT - 1.25 SB. The rate of IHC variance explained by this model, as determined by multiple correlation coefficient square (R2), was 42.6%. These results suggest that CTC provides only gross information about the degree of impairment of liver function in cirrhosis. To evaluate the role of liver function in the prognosis or in the response to treatments, it should therefore be preferable to employ direct measurement of liver function using a clearance technique.

Adult↗
PubMed1985

[Anti-arrhythmia effect of long-term encainide in chronic ventricular extrasystole].

The long term efficacy and tolerance of encainide were studied in 48 patients with chronic/ventricular extrasystoles (VES) treated for 6 months. Holter monitoring was performed before treatment and at each dose increment (75 mg/day; 150 mg/day and 225 mg/day) during the first week of titration, and then after 1 month and 6 months of treatment. The dose administered in the long-term study corresponded to the minimum effective dose during the titration phase (the dose which reduced the number of VES/24 hours by at least 75%). The average number of VES/hour decreased significantly from 480.6 before treatment to 2.0 at the end of the study. The frequency of episodes of ventricular tachycardia decreased significantly during treatment. The commonest side effects were vertigo, visual disturbances and headaches. Treatment was interrupted because of side-effects or inefficacy in 6 patients. The surface ECG showed significant lengthening of the PR, QRS and QTc periods and encainide appeared to have aggravated the ventricular arrhythmias of 4 patients receiving 200 mg/day. The plasma concentrations of encainide and its two principal metabolites were measured during the titration phase, at 1 month and after 6 months of treatment. 15.6 per cent of patients were slow and 84.4% of patients were rapid metabolizers. The wide individual variations of plasma concentrations and the absence of correlation between the plasma concentrations of encainide and its metabolites and the antiarrhythmic effect suggest that the compound and its metabolites play a role in the antiarrhythmic effect of the drug.

Adolescent↗
PubMed1985

[Drug trials in man].

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Clinical Trials as Topic↗
PubMed1985

[Electrophysiological effects of intravenous sotalol. Relation with plasma levels].

The object of this study was to confirm the electrophysiological effects of sotalol, a betablocker which increases the duration of the action potentials of myocardial cells, and to investigate the relationship of these effects with the doses used and plasma concentrations (PC) of the drug. 13 patients (23 to 72 years) were divided into 3 groups: Group 1 (n = 5): 0.6 mg/kg; Group 2 (n = 4): 1.2 mg/kg; and Group 3 (n = 5): 1.8 mg/kg. Measurements were performed before and 35 minutes after starting a 15 minute intravenous infusion of sotalol. At all doses, sotalol decreased the heart rate (HR), increased the corrected sinus node recovery time (CSNRT), prolonged the effective refractory periods (ERPA) and functional refractory periods (FRPA) of the right atrium. Atrioventricular conduction was depressed; prolongation of AH at an imposed rate of 100/min, prolongation of the nodal refractory periods (ERPN and FRPN), and an earlier Wenckebach point. The corrected QT interval (QTc) and ventricular refractory period (ERPV) increased. The QRS complexes and HV intervals were unchanged. Increases of CSNRT, AH, ERPN, FRPN, QTc, and ERPV were observed after the first dose (Group 1). At the dose of 1.8 mg/kg (Group 3) all parameters were modified (except the QRS and HV). All patients increased their ERPV by more than 20 p. 100. The parameters which illustrated the dose-effect relationship were the HR, ERPA, FRPN, and CSNRT. The PC of sotalol measured 60 minutes after starting the infusion were 0.58 +/- 0.23 microgram/ml (Group 1), 0.78 +/- 0.32 microgram/ml (Group 2) and 1.73 +/- 0.43 microgram/ml (Group 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

[Anti-arrhythmic effect of amiodarone in the 24 hours following a single oral loading dose. Clinical and pharmacological study].

This study demonstrated the rapid antiarrhythmic effects of oral amiodarone (Am). A single 30 mg/kg dose was given to 67 patients, 18 with supraventricular arrhythmias (atrial extrasystoles: 11 cases, reciprocating tachycardia: 4 cases, intraatrial reentrant tachycardia: 2 cases, paroxysmal atrial fibrillation, AF: 1 case). Eighteen patients had permanent AF. Thirty-one patients had ventricular arrhythmias (ventricular extrasystoles, VES, isolated or in salvos: 22 cases, and ventricular tachycardia, VT: 19 cases). The effect on atrial extrasystoles was significant 4 to 13 hours after AM and maximal (-98% +/- 3.6%) at 7.7 +/- 1 hours. They recurred in 3 cases at the 18th hour. No significant effects were observed on the other supraventricular tachycardias. The effect on the atrioventricular node (AVN) assessed by the ventricular response to permanent AF, was significant after the 3rd hour and maximal ( = 38 +/- 6 bpm) at the 7th hour. The reduction in the frequency of VES was significant from the 5th to the 19th hour of treatment. Control of VT was obtained in 5 cases between the 3rd and 8th hours. The treatment was well tolerated as no side effects were reported. The plasma concentration (PC) of amiodarone (54 patients) and of N-desethylamiodarone (NDA) (36 patients) were measured; the maximal values were 2.53 +/- 1.5 mg/l for Am and 0.22 +/- 0.1 mg/l for NDA. A 60% decrease in the number of VES was observed with PC of Am of 1.90 +/- 0.3 mg/l and a 20% reduction in the ventricular response to AF at PC of Am of 1.50 +/- 0.33 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

[Pharmacokinetics and plasma concentrations of anti-arrhythmic drugs].

The efficacy of antiarrhythmic drug treatment and the risk of toxicity can be evaluated by studying the relationship between these agents effects and their plasma concentrations. Optimal drug surveillance is not possible, however, unless: an effect-concentration relationship can be demonstrated; therapeutic and toxic plasma concentrations have been established; plasma concentrations in different patients demonstrate adequate dosage when measured after the administration of standard doses; a reliable and specific dosing method can be easily performed at a reasonable cost. Lidocaine, quinidine, and procainamide are among the commonly employed antiarrhythmic agents which fulfill all these requirements. Clinical pharmacologic studies are underway for disopyramide, amiodarone, mexiletine, propafenone and flecainide, and certain findings are already of value in hospital settings.

Anti-Arrhythmia Agents↗
PubMed1983

Kinetics of medroxalol, a beta- and alpha-adrenoceptor antagonist.

Eight healthy men received single oral doses of 400, 800, and 1200 mg medroxalol and a single intravenous dose of 1 mg per kg body weight on four occasions separated by at least 2 wk. Plasma medroxalol concentrations were assayed up to 24 hr after each dose by a specific high-pressure liquid chromatographic assay. Urinary excretion of parent compound was determined as well. Following oral doses medroxalol reached peak plasma concentrations within 2.5 to 3 hr. The t 1/2 of the terminal decay phase was 11.1 hr. Mean apparent volume of distribution (aVD) was between 11.2 and 16.4 l/kg, and mean total body clearance (ClT) was between 0.73 and 0.99 l hr-1 kg-1. Mean urinary recovery of parent drug within 48 hr was 2.3%, 3.9%, and 3.6% after the oral doses compared to 8.2% after the intravenous dose. Bioavailability estimated from AUC was 27.2% after 400 mg, 31.3% after 800 mg, and 37.4% after 1200 mg by mouth. Since aVD, t 1/2, ClT, and urinary excretion did not differ significantly after the three oral doses, medroxalol kinetics appear to follow a dose-linear model.

Administration, Oral↗
PubMed1982

The effects of diltiazem and reduced serum ionized calcium on ischemic ventricular fibrillation in the dog.

Calcium influx blockers reportedly suppress ventricular arrhythmias during acute ischemia. We therefore studied the effects of diltiazem and reduced serum ionized calcium on ventricular fibrillation (VF) in a reversible ligation model. VF was produced at 15-minute intervals by simultaneous occlusion of the left anterior descending and circumflex arteries of 31 dogs. Time from coronary occlusion to onset of VF showed no significant variation during 15 consecutive trials in six dogs that received saline alone. Intravenous infusion of diltiazem (0.02 mg/kg per min) markedly delayed the onset of VF in each of 10 dogs (P less than 0.0001). Mean VF latency increased from 138 to 295 seconds during a 45-minute diltiazem infusion, declined exponentially when the infusion ceased, and was strongly correlated with serum diltiazem concentration (r = 0.96, P less than 10(-6)). In five dogs, hemodynamic measurements, including coronary venous blood flow, were performed during each occlusion. The increase in VF latency by diltiazem was not due to increased coronary flow during occlusion or to reduction of left ventricular (LV) mechanical work. In six dogs, mean serum ionized calcium, [Ca++], was reduced from 1.11 to 0.59 mM by infusion of sodium citrate. Citrate infusion increased mean VF latency from 155 to 243 seconds, and the increase observed in each dog was correlated (r = 0.84, P less than 10(-6)) with the reduction in [Ca++]. VF latency was unaffected by lidocaine in nine dogs. The antifibrillatory effect of diltiazem during global LV ischemia may be an electrophysiological phenomenon related to reduction of cellular calcium influx.

Animals↗
PubMed1981

Beneficial hemodynamic response to chronic prazosin therapy in congestive heart failure.

Thirteen patients with advanced congestive heart failure (CHF) were treated with prazosin. Following the first dose, cardiac output (CO) (mean +/- SD) rose from 3.2 +/- 1.2 to 4.3 +/- 1.1 L/min, pulmonary artery diastolic pressure (PAD) decreased from 23 +/- 12 to 18 +/- 11 mm Hg, mean arterial pressure (MAP) decreased from 85 +/- 10 to 76 +/- 10 mm Hg, and heart rate did not change (92 +/- 15 vs 92 +/- 14 bpm). At the end of a 48 to 72 hour titration to an optimal regimen, significant effects on CO (3.2 +/- 1.1 vs 4.5 +/- 1.3 L/min), PAD (24 +/- 12 vs 18 +/- 8 mm Hg), and MAP (84 +/- 10 vs 76 +/- 10 mm Hg) were still seen. The patients were restudied after 3 months of treatment. In contrast to reports of rapid development of tolerance to prazosin, we found continued beneficial effects on CO (3.0 +/- 1.3 vs 3.8 +/- 1.0 L/min) and PAD (23 +/- 12 vs 18 +/- 10 mm Hg), without significant change in MAP (81 +/- 11 vs 78 +/- 8 mm Hg). We found wide variability in the CO rise in response to prazosin, which was not accounted for by differences in plasma prazosin concentration. Systemic vascular resistance in the untreated state did correlate with the percentage change in CO. In addition, excessive lowering of the PAD appeared to blunt the CO response in some cases.

Blood Pressure↗
PubMed1981

Electrophysiologic effects of N-acetylprocainamide in human beings.

The electrophysiologic properties of N-acetylprocainamide (NAPA) were studied in 10 patients undergoing cardiac catheterization. Each patient received two successive intravenous infusions: one loading infusion over 15 minutes and one maintenance infusion at a slower rate for 30 minutes. Eight patients received 10.5 mg/kg body weight and two received larger doses (16 and 21 mg/kg, respectively). NAPA plasma concentration was measured at 5 minute intervals from 0 to 25 minutes, and then at 15 and 30 minutes of the second infusion. Mean blood pressure and electrophysiologic data obtained by programmed stimulation were recorded before drug administration and at 15 and 30 minutes of the infusion when the concentration of NAPA was nearly constant in each patient (range 12 to 35 microgram/ml). NAPA decreased blood pressure (p less than 0.005), increased corrected Q-T interval (p less than 0.01) and increased the atrial and ventricular effective refractory periods from 267 +/- 40 to 307 +/- 41 ms (p less than 0.01) and from 278 +/- 37 to 301 +/- 32.8 ms (p less than 0.05), respectively. NAPA did not significantly change sinus cycle length or sinus nodal recovery time, conduction intervals (A-H, H-V, P-R, QRS), atrioventricular nodal functional refractory period or nodal Wenckebach cycle length. The patient receiving the largest dose experienced mild nausea when the plasma concentration was above 35 microgram/ml. These data show that the electrophysiology of NAPA in human beings is different from that reported for procainamide. At the plasma concentrations studied NAPA increases atrial and ventricular refractory periods without increasing cardiac conduction times

Acecainide↗
PubMed1981

Clinical pharmacology and antiarrhythmic efficacy of N-acetylprocainamide.

Eleven patients with chronic ventricular arrhythmias took part in a study of N-acetylprocainamide (NAPA), the major metabolite of procainamide, in order to characterize further NAPA's clinical pharmacology and antiarrhythmic action. The frequency of ventricular arrhythmia on 24 hour ambulatory electrocardiographic recordings was comparable on recordings obtained in a prestudy screening, during treatment with placebo before administration of NAPA and after treatment with NAPA. The initial dosage of NAPA was 500 mg every 8 hours, which was increased by 500 mg increments every few days until 90 percent suppression of arrhythmia or intolerable adverse effects occurred. Only two patients achieved 90 percent suppression of ventricular ectopic complexes. The mean plasma concentration associated with 90 percent suppression of arrhythmia in these two patients ws 12.6 and 32.3 mg/ml, respectively. One of these two patients was unable to continue long-term therapy with NAPA because of a rash. Other adverse effects included gastrointestinal symptoms in seven patients with visual symptoms in four patients at plasma concentratons as low as 6.9 mg/ml. NAPA obeyed linear pharmacokinetics over the range of dosages studied (500 to 2,500 mg every 8 hours) and had a half-life of 10.7 +/- 1.98 hours (mean +/- standard deviation). There was no change in the P-R or QRS intervals and there was a dose-dependent prolongation of the Q-Tc interval. It is concluded that in this patient group, NAPA suppressed chronic ventricular ectopic complexes without adverse effects in only a minority of patients.

Acecainide↗