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Biomedical subjects

B Flouvat

Publications and source records attributed to B Flouvat.

At least 37 records · Page 2Linked to original sources
PubMed1991

The effect of food and antacids on lansoprazole absorption and disposition.

Bioavailability of lansoprazole, a new gastric proton pump inhibitor, was investigated in 12 healthy subjects. Each subject received in random order, lansoprazole (30 mg) alone or associated with standard meal or with antacids (aluminium and magnesium hydroxides) or one hour later than antacids. Lansoprazole and metabolite (sulfone (AG 1813), sulfide (AG 1777) and hydroxylated (AG 1908) metabolites) plasma concentrations were determined using a specific high pressure liquid chromatographic assay procedure, with a limit of detection of 2 ng/ml. The time to peak was significantly later with food (p less than 0.001) and its magnitude was significantly decreased (600 +/- 330 ng/ml vs 1151 +/- 344 ng/ml, p less than 0.001). The bioavailability of lansoprazole was significantly decreased by food, about 27%, (p less than 0.05) and slightly decreased by concomitant administration of antacids (NS), the effect was more pronounced in male subjects (p less than 0.05). Lansoprazole is presented as an enteric-coated granules, the concomitant administration of antacids, increasing the gastric pH, increased the absorption rate of lansoprazole. When antacids were administered one hour before lansoprazole, no effect was observed on lansoprazole bioavailability. This study showed that lansoprazole must be administered in fasting state and not simultaneously with antacids.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1991

[Pharmacokinetics of aspirin in African children with normal nutrition and malnutrition].

Pharmacokinetics of aspirin given orally at antipyretic dose (12 mg/kg) were studied in 11 African children aged 4-48 months. In order to examine the influence of nutritional status on aspirin kinetics, children were classified according to Waterlow criteria. Blood samples were collected during the 8 hours following the initial dose. Albumin, prealbumin and transferrin plasma levels were measured and plasma salicylic acid (SA) concentrations determined by a fluorometric method. Nutritional status seemed to have no prominent effect on plasma concentrations of SA. The volume of distribution found in our study was lower than those obtained in other studies. This could be explained by lower plasma aspirin esterase activities in black children. There were large individual variations in plasma salicylate concentrations. For example, even at antipyretic doses, saturation phenomena appeared in two children.

Aspirin↗
PubMed1990

[Treatment with sustained theophylline release. Monitoring by salivary assay in children].

We have tested the possibility of replacing plasma assays by salivary assays of theophylline for the monitoring of sustained-release theophylline therapy in asthmatic children. In a first group of 40 children aged 7.2 +/- 3.3 years (mean +/- SD) treated with sustained-release theophylline in mean daily doses of 18.8 +/- 5 mg/kg, 77 plasma and saliva samples were taken simultaneously 6 hours after the morning dose (6 H). Saliva was collected after mouth-wash and stimulation with 10 mg of citric acid. Assays were performed using the EMIT method. Theophylline plasma concentrations (P) and salivary concentrations (S), both expressed as mumol/l, were found to correlate: P = 1.58 S + 8.7 (P less than 0.0001). In a second group of 33 children, 39 simultaneous samples were taken at 6 H. From the equation previously obtained the plasma concentration corresponding to each salivary concentration was calculated, and the calculated value was compared with the measured value. The difference between the two values was 7.1 +/- 9 mumol/l. On this basis, and because the method is non-invasive and painless, were are now using salivary assays (under strict conditions of collection and measurement) to verify the patients' compliance and to maintain or adjust dosage in asthmatic children.

Adolescent↗
PubMed1990

Development and pharmacokinetics of a new sustained-release formulation of diltiazem.

Among the antihypertensive agents, calcium antagonists and in particular diltiazem play a leading role. To improve the conditions of diltiazem administration in the treatment of hypertensive patients a galenic formulation allowing administration of a single daily dose has been developed. The studies discussed in the following are concerned with the pharmacotechnical and pharmacokinetic development of sustained-release microgranules (sustained-release diltiazem). Bioavailability studies were performed after single-dose administration and after repeated-dose administration which were compared to the conventional formulation of diltiazem, Tildiem. After single-dose administration the following results were achieved: a relative bioavailability of 1.06 +/- 0.35; a prolongation of tmax of 7.16 +/- 2.66 vs. 2.46 +/- 0.80 h; and a longer final half-life of 11.8 +/- 5.3 vs. 5.6 +/- 1.1. After repeated administration of sustained-release diltiazem at a single daily dose of 240 mg compared to repeated administration of the conventional formulation of diltiazem at doses of 120 mg every 12 h over a period of 6 days, the following results were obtained: a relative bioavailability of 0.90 +/- 0.17; a lowering effect on Cmax of 191 +/- 65 vs. 230 +/- 95 ng/ml; statistically equivalent minimum concentrations of 62 +/- 21 ng/ml vs. 74 +/- 33 ng/ml. In an additional study, the effect of concurrent food intake on the bioavailability of diltiazem was confirmed. An increase in bioavailability of 28% in combination with an increase in interindividual variability was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Pharmacokinetic and pharmacodynamic comparison of two doses of long acting propranolol (80 and 160 mg) in healthy subjects.

1. The kinetics and dynamics of long acting propranolol 80 mg and 160 mg were examined after single oral doses to 12 healthy volunteers. 2. Long acting propranolol 160 mg produced a twofold increase in mean peak blood propranolol concentration and AUC compared with the lower dose. There was no difference in elimination half-life, bioavailability and mean residence time of propranolol between the two doses. 3. Resting pulse rate was decreased by long acting propranolol 160 mg but not by the lower dose. 4. Both preparations blocked exercise induced tachycardia during the entire observation period of 29 h. Percentage inhibition of exercise tachycardia was significant at all time points but long acting propranolol 160 mg exhibited a greater reduction at 24 h and 29 h. 5. Increase in systolic blood pressure during exercise was inhibited by both preparations during the entire observation period with no differences between them. 6. The doubling of the dose administered was reflected in blood concentrations but not in pharmacodynamic parameters. Few pharmacodynamic differences were found between the two doses.

Adult↗
PubMed1989

Pharmacokinetics of ketoprofen in man after repeated percutaneous administration.

A topical formulation of ketoprofen, a widely used nonsteroidal antiinflammatory drug, has recently been developed. Ten healthy young subjects (mean age 23.5 +/- 2.5 years) received daily 15 g of 2.5% ketoprofen gel, corresponding to 375 mg on the skin of the back over an area of 750 cm2. Plasma samples were collected after the first dose and after 10 days of chronic treatment. Urine was also collected. Ketoprofen was assayed by HPLC. The peak plasma concentration was 144 +/- 91 ng/ml after the first administration with apparent absorption and elimination half-lives of 3.2 +/- 2.4 h and 27.7 +/- 18.0 h, respectively. The total quantities of ketoprofen eliminated in the urine represented about 2.6% of the first dose applied. At the end of the study, the apparent half-life of unchanged ketoprofen was 17.1 +/- 9.1 h, and there was no accumulation. In this study, no sign of local intolerance was seen.

Administration, Cutaneous↗
PubMed1988

Pharmacokinetic interactions between NSAIDs (indomethacin or sulindac) and H2-receptor antagonists (cimetidine or ranitidine) in human volunteers.

The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2-receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2-receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac.

Adult↗
PubMed1987

Determination of theophylline and its metabolites in plasma and urine by reversed-phase liquid chromatography using an amine modifier.

A high-performance liquid chromatographic method for the determination of the concentrations of theophylline and its metabolites in plasma and urine samples is presented. The method uses the decylammonium ion, an N-alkylammonium modifier, and makes it possible to separate theophylline and its metabolites from other uric acid or xanthine derivatives, especially 1,7-dimethylxanthine, a metabolite of caffeine. The plasma and urine purification procedure is convenient, rapid and reproducible, and it can be used to determine low plasma and urine concentrations.

Acetonitriles↗
PubMed1986

Comparison between theophylline analysis by nephelometric inhibition immunoassay and high performance liquid chromatography.

Rate nephelometric inhibition immunoassay (NIIA) was used to determine 94 serum theophylline concentrations, and these results were compared with those obtained using high performance liquid chromatography (HPLC) as a reference method. The measurements obtained by the nephelometric method were, on the average, 20% higher than those obtained by the chromatographic method (p less than 0.001). The coefficient of variation of the nephelometric method was 12.3%, compared with 3.9% for the chromatographic reference method. In the group of subjects having a serum concentration of caffeine greater than or equal to 0.5 microgram ml-1, the difference in serum theophylline concentration found between NIIA and HPLC correlated with serum caffeine concentration (r = 0.3755, df = 46, p less than 0.01). NIIA theophylline concentration was 8.8 +/- 3.2 micrograms ml-1 in serum from six additional patients receiving theophylline 9.1 +/- 3.4 micrograms ml-1 after adding 10 micrograms caffeine (NS), and 13.1 +/- 3.5 micrograms ml-1 after adding 10 micrograms 1,3-dimethyluric acid (p less than 0.001). We conclude that (a) the results obtained by the NIIA method are more variable and consistently higher than those obtained by the HPLC method and (b) 1,3-dimethyluric acid (a caffeine and theophylline metabolite) is responsible for this overevaluation.

Adult↗
PubMed1986

Pharmacokinetic and pharmacodynamic interactions between nifedipine and propranolol or betaxolol.

Pharmacokinetic and pharmacodynamic interactions between nifedipine and two beta-blocking agents were investigated. Eighty mg propranolol twice daily, and 20 mg betaxolol once daily, were randomly administered orally to six young healthy male volunteers, either singly for four days, or combined with nifedipine for the two subsequent days. Nifedipine had similar effects on the pharmacodynamics of both drugs. Nifedipine significantly enhanced propranolol bioavailability and Cmax, but reduced its tmax, in three out of six subjects who were also good absorbers of beta-blockers when taken alone. These effects might be due to enhanced intestinal absorption and/or enhanced first-pass effect, induced by nifedipine.

Adrenergic beta-Antagonists↗
PubMed1985

Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants.

The purpose of our prospective randomized study was to compare the efficacy of theophylline ethylenediamine and caffeine sodium citrate in the treatment of idiopathic apnea in premature infants. Sixteen infants with three or more severe apneic attacks were studied. Twenty-four-hour cardiorespiratory recordings immediately before and after randomization and four days later showed similar significant decreases of the apnea frequency in both theophylline- (group 1, n = 8) and caffeine-treated infants (group 2, n = 8). No undesirable side effects were observed, except for tachycardia in one infant in group 1. We suggest reasons for preferring caffeine to theophylline in the control of idiopathic apnea in premature infants: caffeine is as efficient and easier to administer.

Apnea↗
PubMed1985

Pharmacokinetics of cibenzoline in patients with renal impairment.

Pharmacokinetic values of cibenzoline, a new, investigational, antiarrhythmic drug, were determined in 13 patients with varying degree of renal impairment, creatinine clearance range between 5 and 53 mL/min. Cibenzoline plasma levels were measured after direct intravenous injection of one single 1 mg/kg dose. The apparent volume of distribution of the drug (276 1) was similar to that reported in healthy subjects. Total body clearance decreased with creatinine clearance, and there was a close correlation between cibenzoline renal clearance and creatinine clearance (r = 0.956; P less than 0.001). Plasma elimination half-life was prolonged, with values ranging from 7:4 to 23.6 hours. This study showed that cibenzoline total body clearance correlated with the degree of renal impairment, and it is suggested that in patients with chronic renal failure dosage should be adjusted according to creatinine clearance values.

Adult↗
PubMed1985

Interactions between smectite, a mucus stabilizer, and acidic and basic drugs. In vitro and in vivo studies.

The interaction of phenylbutazone and diazepam with smectite were studied in in-vivo and in-vitro. The kinetics of both drugs were investigated in healthy subjects after oral administration as monotherapy or in association with smectite. Smectite did not substantially alter the kinetics of phenylbutazone, whereas the peak plasma concentration of diazepam was reduced to 91%, and the time of peak concentration was prolonged by 153% of the control values. The in-vitro investigations were conducted at pH 5.5 and 8 and showed that there was no interaction between phenylbutazone and smectite, but that it adsorbed diazepam. The findings suggest that smectite delays the absorption of basic drugs and does not alter the absorption kinetics of acidic drugs.

Absorption↗