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Biomedical subjects

G Cheymol

Publications and source records attributed to G Cheymol.

At least 73 records · Page 4Linked to original sources
PubMed1987

[Clinical trials of drugs without immediate therapeutic objectives].

Clinical trials without immediate therapeutic objectives are performed in phases I and III of drug testing. In phase I, the studies in a small number of healthy volunteers provide information about tolerance, dosage, pharmacokinetics and often, about the principal effects. In phase III, the therapeutic value of the drug has been demonstrated, and the aims are to determine the circumstances which increase the risk of iatrogenicity. These trial are carried out in elderly patients and in those with hepatic or renal failure. In addition, information about drug interactions may be required for the AMM report. Examples are given to illustrate these principles. The author recall the conditions which must be strictly adhered to in the execution of these trials.

Adult↗
PubMed1986

Quantitative liquid chromatographic determination of sotalol in human plasma.

The analysis of sotalol by a simple and sensitive liquid chromatographic assay is described. Sample preparation involves an extraction by chloroform and isoamyl alcohol (3:1, vol/vol) at pH 9.0 followed by back extraction into 0.05 M sulfuric acid. Analyses are carried out on a reversed-phase chromatographic system using an octadecylsilane stationary phase and a water-methanol-acetic acid-methanesulfonic acid (91.00:8.50:0.50:0.025, vol/vol/vol/vol) mobile phase adjusted at pH 3.3. Sotalol is quantified on the basis of ultraviolet absorption at 235 nm. The precision of the method ranged from 6.3% at 0.16 microM (50 ng/ml) to 3.3% at 5.18 microM (1,600 ng/ml). The limit of quantification was established 0.08 microM (25 ng/ml). This assay provides a suitable method for pharmacokinetic studies.

Chromatography, High Pressure Liquid↗
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

[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

[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

[Hepatitis and pancreatitis due to indalpine].

The authors report two cases of hepatitis and a case of pancreatitis associated with indalpine. In one case of hepatitis, onset was acute and the clinical presentation was suggestive of cholecystitis; in the other case, hepatitis was discovered by biological tests. In the two cases, hepatitis was mainly cytolytic. Outcome was favorable upon interruption of drug administration. Onset of pancreatitis was inconspicuous, with progressively increasing pain. The pancreatic lesions were diffuse and massive. After interruption of administration, outcome was eventually favorable. Elevated amylasemia was also noted in the two cases of hepatitis. It is suggested that transaminase and amylase activities should be monitored during indalpine therapy.

Aged↗
PubMed1984

Study of the bioavailability of pindolol in malabsorption syndromes.

Pindolol kinetics and bioavailability were studied after a single dose (oral 5 mg; intravenous 3 mg) in nine patients with malabsorption (two with villous atrophies, seven with short bowel syndromes) and in six healthy volunteers. After oral administration no significant differences were observed in bioavailability (59.4 +/- 6.2% in patients vs 79.5 +/- 8.6% in controls) and for most plasma and urinary pharmacokinetic parameters between the experimental and control groups as a whole. However, detailed analysis revealed decreased absorption for pindolol in two out of nine patients. After i.v. administration, apparent distribution volume was smaller (V: 2.10 +/- 0.25 l kg-1 vs 3.05 +/- 0.31 l kg-1) and global elimination constant was larger (ke: 1.43 +/- 0.46 h-1 vs 0.56 +/- 0.10 h-1), in patients with malabsorption than in controls (P less than 0.05). The smaller weight of patients and pharmacokinetic modifications due to the pathology could account for this.

Administration, Oral↗
PubMed1984

[Blood pharmacokinetics of fluorine in man after the oral administration of nicomethanol hydrofluoride].

The pharmacokinetic parameters of fluoride have been studied, after a single oral administration to human volunteers of two fluoridated compounds: sodium fluoride, and a new organic fluoride salt, nicomethanol hydrofluoride. The results obtained with these two compounds were very similar, suggesting that no abnormal accumulation of fluoride in the body occurs after using nicomethanol hydrofluoride.

Administration, Oral↗
PubMed1983

Estimation of the absolute oral bioavailability of pindolol by two analytical methods.

The absolute oral bioavailability of pindolol has been estimated by two analytical methods, fluorimetry and GLC-ECD. The study was carried out in six healthy subjects who received either i.v. or oral pindolol in random order. The results obtained by both methods were similar and confirm the high bioavailability (about 75%) of pindolol. The present findings are compared with previous publications and emphasize the importance of undertaking bioavailability studies in the same subjects.

Administration, Oral↗
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↗
PubMed1983

[Evaluation of pindolol absorption in malabsorption syndromes].

Reports on drug absorption in intestinal diseases are scarce. To investigate pindolol absorption, a drug particularly well absorbed and with low hepatic extraction, plasma concentrations and 54-h urinary excretion (after both oral and intravenous dose) were studied in 6 healthy volunteers and 13 patients with intestinal malabsorption (coeliac disease 5 cases, short bowel syndrome 8 cases) after an overnight fasting. Pindolol plasma concentrations were almost identical after a single intravenous dose in both patients and controls. Again mean blood levels after an unique oral dose were not significantly different between the two groups. However, absorption was slow and/or delayed in eight out of thirteen patients and overall absorption was decreased in two of them. These abnormalities might be related to the diseased intestine, since plasma concentrations and urinary excretion following intravenous administration were quite similar to those observed in volunteers. Nevertheless, results were not related to the extent of the intestinal disease nor the degree of impairment of small intestinal function.

Administration, Oral↗