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Biomedical subjects

A Durand

Publications and source records attributed to A Durand.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Determination of nifedipine in plasma by a rapid capillary gas chromatographic method.

A rapid, specific and reliable gas chromatographic assay procedure for Nifedipine in plasma has been developed. With a single-step solvent extraction, and electron capture detection, the method is sensitive to 0.5 ng/mL of plasma and the standard curve is linear from 0.5 to 500 ng/mL. Samples are protected from light to prevent formation of photodecomposition products. The method has been used to monitor drug concentrations in patients receiving therapeutic doses.

Chromatography, Gas↗
PubMedDate not supplied

A preliminary metabolic study of alpidem in rat and man.

The metabolism of alpidem, a new anxiolytic agent in the chemical series of imidazopyridines, was investigated in rat and man. In both species the compound is extensively metabolised by three main routes of biotransformation: aromatic oxidation of the imidazopyridine ring; n-dealkylation; and/or aliphatic oxidation of the substituted amide side chains.

Adult↗
PubMedDate not supplied

A rapid HPLC procedure for the simultaneous determination of chloroquine, monodesethylchloroquine, diazepam, and nordiazepam in blood.

Chloroquine, monodesethylchloroquine, diazepam, and nordiazepam levels are simultaneously determined in whole blood or plasma by HPLC. Papaverine is used as internal standard, and the analysis is performed after protein-binding hydrolysis, absorption on Extrelut, and elution with diethyl ether/methylene chloride (70:30 v/v). UV detection is used at 343 nm for 12 min, then changed to 242 nm. There are two mobile phases with two flow rates. The procedure requires 30 min, is reproducible, sensitive (8-10 ng/mL for chloroquine and its metabolite, 4 ng/mL for diazepam and nordiazepam), and selective, especially towards other antimalarial agents and drugs like adrenaline or barbiturates, which may be used in chloroquine poisoning therapy. It can be used for pharmacokinetic studies, therapeutic control, to establish the diagnosis and prognosis of a chloroquine poisoning, and to follow and optimize treatment.

Chloroquine↗
PubMedDate not supplied

Pharmacokinetic and pharmacodynamic analysis of sedative and amnesic effects of lorazepam in healthy volunteers.

This study describes for the first time the pharmacokinetic and pharmacodynamic modeling of the psychomotor and amnesic effects of a single 2-mg oral dose of lorazepam in healthy volunteers. Twelve healthy volunteers were included in this randomized, double-blinded, placebo-controlled two-way crossover study. The effect of lorazepam was examined for a battery of tests that explored mood, vigilance, psychomotor performance, and memory. The pharmacokinetic and pharmacodynamic modeling of these tests was performed using the indirect response model. Vigilance and psychomotor performance were significantly impaired. Short-term memory was not affected, but a paradoxical tendency to improvement of the score was observed 0.4 hours after drug intake. Significant impairment was observed for immediate and delayed cued verbal recall, for immediate and delayed free recall, and for picture recognition as well as for visual-verbal recall, but not for cued visual-spatial recall or priming. Globally, the different effects were greatest between 0.4 to 3 hours after dosing. However, the time course profile of the recovery period suggests a possible dissociation between the kinetics of the effects of lorazepam on vigilance, psychomotor performance, and visual episodic memory, on the one hand, and on verbal episodic memory, on the other. The pharmacokinetic and pharmacodynamic model used two compartments with first-order absorption to describe the lorazepam concentrations and an indirect response model with inhibition or stimulation of Kin to describe the effects. The mean values for calculated median effective concentration (EC50) derived from the pharmacokinetic and pharmacodynamic modeling of the different tests ranged from 11.3 to 39.8 ng/mL. According to these EC50 values, lorazepam seemed to be more potent on the delayed-recall trials than on the immediate-recall trials; similar observations were made concerning the free-recall versus cued-recall trials. The previously stated results suggest that the tests performed in this study represent sensitive measurements of the effects of lorazepam on the central nervous system. Moreover, the parameter values derived from pharmacokinetic and pharmacodynamic modeling, especially, the EC50 values, may provide sensitive indices that can be used to compare the central nervous system effects of benzodiazepines.

Adolescent↗
PubMedDate not supplied

Kinetics of plasma and tissue distribution of 9-cis-retinoic acid in rat.

The biotransformation and tissue distribution of 9-cis-retinoic acid was investigated in hairless rats. Indeed, only limited information is available about the pharmacokinetics of 9-cis-retinoic acid. Assuming that the target site for retinoids is the skin, tissue distribution study is therefore particularly justified. Following single oral administration of 30 mg/kg of 9-cis-retinoic acid, the parent drug and five metabolites were detected in plasma. Additionally, concentrations of 9-cis-retinoic acid and metabolites were determined in the skin and seven other tissues. The distribution of 9-cis-retinoic acid was rapid in all of the organs studied (T(max) </=2 h). In skin, unchanged 9-cis-retinoic acid was still measurable up to 168 h after administration and was undetectable in other organs and plasma after 48 h.

Alitretinoin↗
PubMedDate not supplied

Pharmacokinetics of intrapleural cisplatin for the treatment of malignant pleural effusions.

We determined the toxicity and pharmacokinetics of high-dose intrapleural cisplatin (CDDP) as a treatment of malignant pleural effusions (MPE). Fourteen patients with MPE were enrolled in this study. After complete drainage of the fluid, a catheter was inserted into the pleural cavity during a thoracoscopy. CDDP (300 mg) was administered via the catheter in a 6-h infusion. Peak levels, the areas under the concentration curve (AUC), and drug half-lives were measured in pleural fluid and plasma samples collected at 0 (baseline), 6, and 24 h as well as 4, 14, and 21 days after intrapleural administration. The dosage of CDDP ranged from 153 to 203 mg/m2. The time interval between infusion was prolonged until a maximum of 109 days. Only 7/40 infusions were associated with adverse effects in 4 patients (18%). Residual concentrations in pleural fluid (0.66+/-0.07 microgram /ml) were three-fold higher than in plasma (0.13+/-0.07 microgram/ml). In pleural fluid, maximal concentration (Cmax) varied from 19 to 900 microgram/ml and in plasma from 0.34 to 3.65 microgram/ml. AUC in plasma during the three courses was 112+/-49 microgram/ml/d. The T1/2 was 31+/-33 days higher than that previously reported after intravenous administration (8-15 days). Although intrapleural CDDP has the potential advantage of treating the underlying malignancy in addition to controlling the malignant effusion with a good tolerance, it cannot be recommended for the standard control of malignant pleural effusion. Indeed we observed a great variability of intrapleural CDDP concentration depending on the extent of pleural invasion and plasma diffusion. Further studies are needed to determine the value of high-dose intrapleural CDDP for the treatment of MPE.

Aged↗
PubMedDate not supplied

Phase II study of a combination of cisplatin, all-trans-retinoic acid and interferon-alpha in squamous cell carcinoma: clinical results and pharmacokinetics.

UNLABELLED: Preclinical and clinical data suggest a certain antitumor efficacy for combination of retinoids, cytokines and cytotoxic compounds. PATIENTS AND METHODS: Between November 1994 and October 1996, 38 patients with advanced squamous cell carcinoma were enrolled in a phase II study to investigate an association of low-dose all-trans-retinoic acid (tRA) (40 mg/m2/day, 84 days), interferon-alpha (IFN-alpha) (6.10(6) UI/day, 84 days s.c.) and cisplatin (40 mg/m2/day, day 1, 28 and 56, i.v.). A Pharmacokinetic evaluation was performed on 12 patients. RESULTS: The incidence of grade 3/4 hematologic toxicities was moderate (< 20%). Extra hematological toxicities were frequent but easily manageable and not life threatening. However, treatment delivery was poor since only 6 patients (16%) received full therapy. Seven objective responses were observed (21%), suggesting some degree of synergism between tRA, IFN-alpha and cisplatin. Interestingly, continuous tRA treatment in combination with IFN-alpha and cisplatin did not induce a significant decrease in plasma levels, as had been previously described. CONCLUSIONS: Regarding the short median response duration and the frequency of toxic events, this regimen should no longer be recommended in pretreated patients with advanced disease. However, the consistent response rate reported here may warrant further investigation in an early setting.

Adult↗
PubMedDate not supplied

[Surgical treatment of calcanear fractures (103 cases). Reconstruction-arthrodesis, or reconstruction (author's transl)].

In a twelve-year period, 103 calcanear fractures (thalamus) were operated on, either by the Stulz procedure (calcanear Reconstruction-subtalar Arthrodesis [83 cases]), or by Reconstruction (20 cases). During the first seven years, the Stulz procedure had been performed systematically. During the following five years, indications were shaded between 28 reconstruction-arthrodesis and 20 reconstructions. A complete preoperative radiological study, including especially horizontal calcanear tomography enables to precise what type of injuries affects the four different parts of the calcaneus, and to choose between either procedure.

Adolescent↗
PubMedDate not supplied

The disposition and pharmacokinetics of alpidem, a new anxiolytic, in the rat.

The autoradiographic distribution, disposition, biliary excretion, and pharmacokinetics of alpidem in Sprague-Dawley rats were evaluated after iv or oral administration. Following i.v. administration, autoradiography showed that radioactivity was preferentially localized in lipid-rich tissues including central nervous system structures. After a 3-mg.kg-1 i.v. or oral dose of [14C]alpidem, more than 80% of the radioactivity were excreted in the feces over a 6-day period. Biliary excretion of radioactivity in vigile rats, about 74% of the dose over a 7-hr period after either iv or oral administration, showed that alpidem was well absorbed. The absolute bioavailability (13%) data indicated a high first-pass effect. Plasma pharmacokinetic parameters of alpidem were as follows: Vd = 5 liter.kg-1, Cl = 2.2 liter.h-1.kg-1, and terminal t 1/2 beta = 1.2-1.7 hr. Three metabolites with a pharmacological activity similar to that of alpidem were detected in plasma. They were eliminated from the central compartment with half-lives comparable to that of the parent drug. Alpidem crossed the blood-brain barrier following either i.v. or oral administration, resulting in cerebral levels 2.5 to 4 times greater than the plasma levels. Alpidem was eliminated from the central nervous system according a biphasic process with a t 1/2 alpha comparable in plasma and brain. Alpidem represented 94 and 63% of cerebral radioactivity 5 min after i.v. and oral administration, respectively. Two out of the three active plasma metabolites were detected in the brain.

Administration, Oral↗
PubMedDate not supplied

[Plasma levels of metapramine and its 3 major metabolites in patients with depression. Results and preliminary interpretations].

Metapramine (Timaxel) and his three major metabolites (19148 RP, 23669 RP, 19749 RP) have been determined in the plasma of 18 depressed inpatients treated by the antidepressant drug (12 women and 6 men; 7 are smokers and 11 non-smokers). In a steady state, interindividual variability is very important, especially for 23669 RP. No significant correlation exists between normalized doses (mg.kg-1) and normalized plasma concentrations (ng.ml-1/dose mg.kg-1) of metapramine or anyone of its metabolites. The plasma metabolic ratios reveal also important intraindividual and interindividual variability. Two populations of patients seem to exist: extensive metabolizers and relatively poor metabolizers, without apparent clinical consequence because 23669 RP shows an antidepressant activity. Women seem, with equal normalized doses, to exhibit higher plasma levels of unchanged metapramine than men, due to a lower protein-binding rather than to a more active metabolism. In patients who received a poly-medication smoking seems not to induce desmethylation of metapramine. The plasma metabolic ratios, compared by the analysis of variance and the Wilcoxon distribution-free test, are significatively influenced by sex and not by tobacco-smoking.

Adult↗
PubMedDate not supplied

[Determination of the optimal dose of bromazepam in the elderly].

The aim of our study was to determine in patients over 70 years, the optimal dose of Bromazepam. Seven patients were administered a unique dose of Bromazepam (3 mg), then repeated doses (1.5 mg) every 12 hours for 9 days. Cmax was 42.5 +/- 12 ng/ml in Tmax ranged from 2 to 12 hours after the first dose-concentrations of Bromazepam at steady-state were between 79 and 157 ng/ml. Half life was 30.5 +/- 14.7 hrs for the unique and the repeated doses. Sleeping was noted for concentrations over 40 ng/ml. The dose of 1.5 mg bid is recommended in old patients.

Administration, Oral↗