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Biomedical subjects

B Flouvat

Publications and source records attributed to B Flouvat.

At least 55 records · Page 3Linked to original sources
PubMed1985

Hemodynamic and pharmacokinetic study of propranolol and atenolol in cirrhosis patients.

The pharmacokinetic properties of propranolol and atenolol were evaluated both in 9 patients with cirrhosis and in 12 healthy subjects. The hemodynamic effects of the drugs were evaluated separately in the cirrhotic patients. Propranolol and atenolol significantly decreased wedged hepatic venous pressure and cardiac output in cirrhotic patients. Propranolol Cmax, tmax and AUC were significantly increased and plasma half-life was significantly prolonged in cirrhotic patients. In contrast, the corresponding pharmacokinetic values of atenolol were not significantly different in cirrhotic patients and in healthy subjects.

Adult↗
PubMed1984

Metronidazole kinetics in patients with acute renal failure on dialysis: a cumulative study.

Nine patients with acute renal failure who were undergoing dialysis at intervals depending on clinical state were injected with metronidazole, 7.5 mg . kg-1 iv every 8 hr. Plasma samples were drawn during the 8 hr after the first infusion, during the first dialysis session, and during the course of the fourth infusion after the first three dialysis sessions. Metronidazole and its two main metabolites (alcohol [M1] and acid [M2]) were assayed by HPLC. The plasma t 1/2 of metronidazole (6.8 hr) is of the same order as that in healthy subjects. M1 and M2 plasma levels increased continuously until the next infusion. Dialysis clearances of metronidazole and its metabolites were about 60 ml . min-1; 25% of metronidazole in the body at the beginning of hemodialysis was eliminated. The corresponding apparent t 1/2 s are 3.3 hr (metronidazole), 8.0 hr (M1), and 7.9 hr (M2). In patients with acute renal disease under hemodialysis, there was no cumulation of metronidazole and its metabolites; hence there is no need for change in dosage regimen.

Acute Kidney Injury↗
PubMed1984

The effect of antacid and aspirin on the bioavailability of isofezolac in man.

Bioavailability of isofezolac, a new non-steroid anti-inflammatory drug, with or without antacid and aspirin coadministration was investigated in 6 healthy volunteer. Each subject received, in random order, isofezolac (50 mg) alone or associated with aspirin (1 g) or phosphalugel (11 g aluminum phosphate). Isofezolac plasma concentrations were salicylic acid by spectrofluorimetric method. Plasma protein binding of drugs was studied by dialysis equilibrium method. During the absorption phase isofezolac plasma levels were slightly decreased in association with isofezolac-aspirin, but bioavailability of isofezolac was not modified. Time to peak of isofezolac was comparable in the three treatments, as was the case with plasma half-lives. Aluminum phosphate did not modify isofezolac availability. Plasma protein binding of isofezolac was very high (99%) and did not influence salicylic acid binding.

Adult↗
PubMed1983

[Pharmacokinetic profile of a slow-release ketoprofen preparation].

Kinetics of ketoprofen release in man from a sustained-release preparation (150 mg) and from capsules (3 X 50 mg) were studied comparatively in 10 healthy adults. Bioavailability of the slow-release preparation is similar to that of capsules : surfaces under the serum concentration curves and urinary elimination were found to be identical. In the sustained-release preparation the immediately available layer (75 mg) ensures achievement of maximal serum concentrations amounting to 59% of those obtained with capsules, after the same time interval. The slow-release layer (75 mg) produces higher serum concentrations from the third hour on, justifying administration of the formulation in two daily doses.

Capsules↗
PubMed1983

[Ketoprofen-aspirin interaction].

Eighteen patients with chronic inflammatory joint disease were treated for two successive five day sequences, in a double blind crossover study, with 300 mg per day ketoprofen given alone or combined with 1,500 mg aspirin. Bioavailability and pharmacokinetics of total serum ketoprofen studied in eight patients did not appear to be significantly modified by addition of aspirin. Measurements of Ritchie's articular index and Lee's functional index demonstrated that ketoprofen was clinically as effective when given alone as in association with aspirin. Measurement of the sedimentation rate by the sigma ESR technique showed that aspirin produced a marked reduction of the antiinflammatory biological activity of ketoprofen which did not however reach statistical significance. This study of interactions between ketoprofen and aspirin shows that it is useless and perhaps harmful to combine the two medications.

Aspirin↗
PubMed1983

Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination.

The pharmacokinetics of acebutolol and hydrochlorothiazide (HCT) alone or in combination were studied in 12 healthy subjects in a cross over study. Acebutolol and diacetolol (the main metabolite) in plasma and urine were determined by HPLC and hydrochlorothiazide by GLC. The main pharmacokinetic parameters of acebutolol did not differ significantly: AUC 4492 +/- 272 micrograms l-1h given alone versus 4118 +/- 354 micrograms l-1h with HCT, half-life (7,69 +/- 0,32 h vs 8,10 +/- 0,72 h) and renal clearance (13,1 +/- 0,5 lh-1 vs 13,8 +/- 0,9 lh-1), respectively. There was no difference in diacetolol pharmacokinetics. HCT values were not significantly different: AUC 784 +/- 48 micrograms l-1h given alone and 720 +/- 42 micrograms l-1h with acebutolol, t 1/2 (4,79 +/- 0,37 h vs 4,73 +/- 0,43 h). The renal clearance was slightly higher when HCT was given with acebutolol (26,2 +/- 2,6 vs 20,3 +/- 2,1 lh-1, p less than 0,05). This increase, observed during the first four hours, was probably due to competition between the drugs for binding to red blood cells.

Acebutolol↗
PubMed1983

Pharmacokinetics in man of a new antiarrhythmic drug, cibenzoline.

The kinetics of cibenzoline (UP 339.01), a new antiarrhythmic drug, was studied after i.v. and oral administration to 5 healthy subjects. Cibenzoline levels in plasma and urine cibenzoline were measured by a GLC method. After i.v. administration, the total clearance was 826 ml . min-1. The fraction of cibenzoline excreted unchanged in the urine was 0.602 and it was correlated with the creatinine clearance. After i.v. and oral administration, the renal clearances were 499 ml . min-1 and 439 ml . min-1, and the half-lives were 4 h 01 min and 3 h 24 min, respectively. The differences were not significant. Availability by the oral route was 0.92, the maximum plasma concentration being observed at 1 h 36 min. The results were compared with those for other antiarrhythmic drugs.

Administration, Oral↗
PubMed1983

Pharmacokinetics of a sustained-release trimazosin tablet formulation.

Pharmacokinetics and bioavailability of a trimazosin sustained-release tablet (SRT) formulation (300 mg) were studied in healthy volunteers. In the first study of 12 subjects, the bioequivalence of trimazosin, 100 mg, in a standard tablet (ST) and in a capsule was demonstrated. After that, the bioavailability of one SRT (300 mg) was compared with that of the STs, (100 mg three times a day), in 19 subjects. Maximum plasma concentration (Cmax) after SRT (8.1 +/- 3.0 mg/L) was significantly lower than that observed after ST (13.5 +/- 2.3 mg/L), time to peak was strongly delayed by a factor 7, and the time when plasma concentrations were higher than half of Cmax (t Cmax/2) was longer (10.4 +/- 3.2 vs 2.3 +/- 0.6 hours, p less than 0.001). Bioavailability of the SRT (300 mg) as measured by the area under the curve (AUC00) was about 65% of the ST. At the seventh dose, after single daily doses of the SRT in 12 subjects, the mean Cmax values were not significantly higher than after the first dose (8.6 +/- 3.2 mg/L vs 7.7 +/- 2.2 mg/L), t Cmax/2 values were the same (10.4 hours), and the AUC0-24 hr was comparable to AUC00 calculated after the first dose. Steady-state plasma concentration of trimazosin was obtained rapidly. No accumulation of trimazosin or its metabolite occurred.

Adolescent↗
PubMed1983

Hypertension in pregnancy: evaluation of two beta blockers atenolol and labetalol.

There is a major controversy over the relative value of anti-hypertensive drugs in hypertension in pregnancy. Our purpose was to study two different beta-adrenolytic drugs, atenolol, a cardioselective beta blocker, and labetalol, an alpha-beta blocker. Fifty-six hypertensive (BP greater than 140/90 mmHg) pregnant women were treated either with atenolol or labetalol. The patients were divided into two subgroups for which there were no statistical differences with regard to age, number of previous pregnancies, initial level of blood pressure and uricemia, proteinuric pre-eclampsia, beginning of therapeutic trial and delivery. The average daily dosage was 144.6 +/- 47.8 mg day-1 with atenolol and 614 +/- 47.8 mg day-1 with labetalol. This study shows: the same anti-hypertensive effect of the two drugs with control of blood pressure in 82% of the cases; a birth-weight significantly higher with labetalol (3280 +/- 555 g) than with atenolol (2750 +/- 630 g) (P less than 0.001); two still-births with atenolol; no adverse effects of the drugs during pregnancy and the neo-natal period; the trans-placental passage of atenolol and labetalol as shown by plasma dosages in the mothers and the new-born. It is concluded that atenolol and labetalol are safe and they are usually effective in the control of the hypertension complicating pregnancy. But labetalol appears to be better able to prevent the appearance of fetal growth retardation.

Adolescent↗
PubMed1983

Pharmacokinetics of ketoprofen in the elderly.

Pharmacokinetic constants of ketoprofen (Orodis, Profenid) were determined in 10 young adults (24.9 +/- 1.3 years) and seven elderly patients (86.3 +/- 2.4). Following oral administration of a 150 mg dose of ketoprofen, no difference in tmax was observed between the two groups. However, compared with younger subjects elderly patients showed a significant increase in t1/2,z (2.72 +/- 0.22 vs 1.77 +/- 0.16 h; P less than 0.01) and AUC (70.4 +/- 6.4 vs 29.13 +/- 2.02 mg l-1 h; P less than 0.001), a non-significant reduction of Vd/F per kg bodyweight (0.145 +/- 0.016 vs 0.213 +/- 0.028 l kg-1) and a decrease in total clearance CLT/F (0.037 +/- 0.002 vs 0.071 +/- 0.004 l h-1 kg-1, P less than 0.05). These results suggest that the glucuroconjugation of ketoprofen is slowed down by age.

Adult↗
PubMed1983

A pharmacokinetic study of acebutolol in aged subjects as compared to young subjects.

Pharmacokinetics of acebutolol have been studied in hypertensive aged patients (79.4 +/- 3.8 years) and in young healthy subjects (23.4 +/- 0.7 years) after intravenous (0.35 mg/kg bolus) and oral administration (400 mg). Acebutolol and diacetolol, the main metabolite, plasma levels were determined by high-pressure liquid chromatography. After intravenous administration, apparent volume of distribution (1.5 vs. 2.4 liter . kg-1, p less than 0.05) and total body clearance (6.2 vs. 8.8 ml . min-1 . kg-1, n.s.) of acebutolol are smaller in elderly than in young men. After oral administration, maximum plasma levels (28.03 vs. 9.68 micrograms . l-1 . kg-1) and area under the curve (163.1 vs. 57.5 micrograms . l-1 . h . kg-1) are significantly higher in aged patients than in young subjects (p less than 0.001). Acebutolol and diacetolol plasma half-lives increase in elderly patients (11.6 vs. 7.2 h and 14.8 vs. 12 h respectively). These results suggest a possible accumulation of acebutolol and diacetolol in elderly.

Acebutolol↗
PubMed1983

Pharmacokinetics of tinoridine after oral administration to healthy subjects and patients with renal failure.

The pharmacokinetics of tinoridine was studied after oral administration (200, 400, and 800 mg in random order) to six healthy subjects and (200 mg) to patients with renal disease. Plasma concentrations of tinoridine were determined by GLC with electron-capture detection and urine concentrations by HPLC. The plasma half-life of tinoridine was about 8.2 h in healthy subjects and was not affected by renal failure. Total body clearance (Clc/F) was very high, but renal clearance was small, about 0.30 1.h-1. There was no correlation between dose (200 mg vs 400 or 800 mg) and Cmax or AUC, suggesting a first-pass effect. Renal failure did not affect pharmacokinetic parameters. However, there was a strong linear correlation between Cmax and age (r = 0.919) and AUC and age (r = 0.838). These results suggest an increase of bioavailability in the elderly.

Administration, Oral↗
PubMed1983

[Effect of 2 beta-blockers on arterial hypertension during pregnancy. Results of a prospective study on 56 pregnant hypertensive women treated with atenolol and labetalol].

This study reports the results that were obtained in 56 cases of arterial hypertension in pregnancy solely by beta-blocking with Atenolol or Labetalol. Any pregnant woman whose arterial blood pressure rises to or exceeds 140/90 mm mercury in two successive examinations at intervals of 8 days with rest is considered to be hypertensive. As soon as treatment is started mothers' supervision is assured regularly by clinical and biological examinations and the dose of drug is adapted to each case. Fetal monitoring is ensured by ultrasound, cardiac rhythm tracings and hormone estimations. As far as the newborn is concerned, blood sugar and electrocardiogram measurements are taken to add to the normal examination at birth. Finally plasma levels of beta-blockers are estimated at birth in the mother and in the cord blood. The analysis of these results shows: for the mother: a fairly constant antihypertensive effect which is about the same for either drug in pregnancy. Further complementary injection therapy was needed, however, in 8 cases in labour. There were alterations in the method of delivery and in particular the Caesarean section rate rose to 12.5% and induction had to be carried out more frequently, triggered off by the slightest sign of fetal distress. As far as the child was concerned: 2 died in utero, the Apgar score was comparable to a control series, there was no bradycardia or broncho-spasm or teratogenic effect, mean weight at birth was significantly higher with Labetalol (3280 g +/- 555) than with Atenolol (2750 g +/- 630), the blood sugar levels at birth were in six cases lower than 1.4 mmol (0.25 g/l) but these were easily pu right by transfusion. The plasma levels of beta-blockers showed that there was a linear relationship between the maternal and fetal concentrations which confirmed that the two molecules pass through the placenta. This study confirms therefore that it is worth while using beta-blockers in cases of hypertension in pregnancy so long as careful observation is carried out, and it seems that the alpha constituent of Labetalol has advantages over the other.

Adolescent↗
PubMed1982

Antihypertensive effect of diacetolol in essential hypertension.

1 Diacetolol is the N-acetylated metabolite of acebutolol and possesses beta-adrenergic receptor blocking properties. 2 Its antihypertensive action was assessed in accordance with a double-blind randomised cross-over scheme in 17 patients with moderate essential hypertension previously well controlled with acebutolol. 3 Significant reductions in lying mean arterial blood pressure were observed with daily doses of 200 mg (- 9%), 400 mg (- 10%) and 800 mg (- 14%), and were associated with significant decreases in heart rate and plasma renin activity. 4 The diacetolol mean plasma level measured 8 to 10 h after drug ingestion was proportional to the dose (207 +/- 27, 394 +/- 63 and 823 +/- 135 ng/ml for respectively 200, 400 and 800 mg/day).

Acebutolol↗
PubMed1982

The beta-blocking effect of diacetolol in humans and its relationship to plasma levels.

The beta-blocking action of diacetolol was studied in six healthy subjects after oral administration of placebo, 200, 400, and 600 mg diacetol in random order by means of exercise tests. Diacetolol plasma levels were determined by the HPLC method. Drug administration had No significant influence on resting heart rate and resting systolic or diastolic blood pressure. The beta-adrenoreceptor blockade was expressed as percentage reduction of exercise heart rate (delta FC%). This value increased with the size of the dose. There was a linear relationship between delta FC% and log plasma levels of diacetolol for each subject, except one. Analysis of variance did not provide a common regression line for all subjects.

Acebutolol↗
PubMed1982

[Pharmacokinetics of theophylline and circadian rhythm].

In the purpose to evaluate the circadian changes of theophylline pharmacokinetic, 8 healthy subjects (age range 22-39 y, weight 54-91 kg) were given a single oral dose of 4,5 mg/kg theophylline solution. Administration was made randomly at 9 a.m. after 12 hours fasting and at 9 p.m. After evening administration the subjects remained awake during the night and a standardized meal was served 4 h and 9 h after theophylline intake. Plasma theophylline concentrations were measured by a high performance liquid chromatography. Absorption is significantly faster in the morning than in the evening but C max values were identical. Plasma elimination half-life is significantly different (8,01 +/- 1,95 h in the morning, 6,23 +/- 1,75 h in the evening). No significant modifications were observed of the area under the curve, the body clearance, the apparent volume of distribution. There were no differences in the total body clearance, the area under the concentration-time curve, the apparent volume of distribution.

Adult↗