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C Larousse

Publications and source records attributed to C Larousse.

At least 19 recordsLinked to original sources

Quantitation of amphotericin B in plasma by second-derivative spectrophotometry.

A method is described for determining amphotericin B in plasma using second-derivative spectrophotometry after deproteinization. The assay was based on the absorbance at 407.5 nm. The second-derivative spectrum recorded between 350 and 450 nm allowed identification of the analyte and showed absence of drug interference. Only bilirubin interfered at high concentration (> or = 50 mumol l-1. The linear concentration ranges were 0.05 -5.0 mg l-1 (r = 0.999, slope = 2.731, intercept = 0.008). Between-day CV < or = 9.7%, within-day CV < or = 5.5%, analytical recovery close to 100% were suitable for clinical investigations. This method provides better specificity than direct absorbance, is simpler and faster than a high performance liquid chromatography assay and can be used routinely by any laboratory possessing a spectrophotometer with a derivative accessory.

Amphotericin B↗

[French system of drug surveillance].

The French drug surveillance system is characterized by: a network of thirty one regional drug surveillance centres, located to provide convenient proximity to health care professionals; a causality assessment method, compulsory for all persons involved in drug surveillance, to assess the causal relationship between an adverse effect and one or more drugs; if necessary, an additional evaluation of the causal relationship will be performed using pharmaco-epidemiology methods; a Technical committee and a National Commission of Drug Surveillance which centralize and assess all the data in order to provide a consensual advice to the relevant authorities on necessary measures, to prevent, or reduce a drug related adverse effect; in the case of an inquiry, the drug surveillance department of the pharmaceutical company and the network of regional drug surveillance centers will pool their data with the aim to exchange information and ideas.

Adverse Drug Reaction Reporting Systems↗

A pilot study of 220 mg/m2 melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity.

We studied the pharmacokinetics and toxicity of 220 mg/m2 melphalan (HDM 220) followed by autologous stem cell transplantation in 16 patients with advanced haematological malignancies. Pharmacokinetic parameters (mean values of steady-state volume of distribution 14.6 l/m2, total body clearance 313 ml/min/m2, elimination half-life 46 min) were the same as those of 140 or 200 mg/m2 melphalan in previous reports. HDM 220 was feasible. Extramedullary toxicity was mainly W.H.O. grade 4 mucositis (13/16 patients). The median duration of 41 d (10, not reached) of thrombocytopenia < 25 x 10(9)/l was long. In multiple myeloma the response rate was 89% in heavily pretreated patients, suggesting that HDM 220 could be considered earlier in the course of the disease as an alternative consolidation therapy.

Adolescent↗

[Neutropenia caused by acenocoumarol associated with hairy cell leukemia].

We report the case of a woman splenectomized to treat her hairy cell leukemia (at the moment in remission) 11 years before the detection of neutropenia. The neutropenia began just after the treatment of pulmonary embolism by acenocoumarol. The neutropenia disappeared quickly after substitution of acenocoumarol by fluindione. We discuss the attribution of the neutropenia to acenocoumarol and the part played by hairy cell leukemia.

Acenocoumarol↗

[Determination of plasma retinol and alpha-tocopherol by HPLC].

Retinol (vit A) and alpha-tocopherol (vit E), the active compounds of vitamins A and E, were assayed by reversed-phase high performance liquid chromatography (HPLC) (C18) with UV absorbance detection at 280 nm. Plasma was deproteinized and liquid-liquid extraction performed with hexane. After evaporation, the residue was dissolved in organic solvents (ether:methanol 25:75, V/V). Standard curves were prepared by adding known amounts of standards to plasma. The use of acetonitrile in the mobile phase (acetonitrile:methanol:water 64.5:33:2.5, V/V) avoided interference peaks, giving a total run time of 8 min. Analyte stability required that samples be treated in the dark. Analytical performance was good: recovery around 100%, detection limits 0.015 mg/l for vit A and 0.030 mg/l for vit E, linear range 2 mg/l for vit A and 20 mg/l for vit E, no recorded interference, and between-run and within-run precision with coefficients of variation < 11%. Analytes were stable at room temperature for 24 h (vit A) and 48 h (vit E) in plasma stored in the dark for one month at -20 degrees C. The standard solution containing both vit A and vit E increased vit A stability. Plasma concentrations (mg/l) for vit A and E were respectively: 0.63 +/- 0.17 and 9.61 +/- 3.1 in adults (n = 29), 0.39 +/- 0.17 et 7.10 +/- 2.41 in children 0 to 15 years (n = 21). This method allows regular monitoring of patients with cystic fibrosis to check for retinol and alpha-tocopherol deficiencies. The usefulness and results of the method are discussed in terms of previous studies.

Adolescent↗

Effects of administration route on pharmacokinetics of viloxazine in the rabbit.

The absorption of viloxazine chlorhydrate was investigated in ten rabbits. Each animal received the drug (15 mg/kg) by three routes: intravenous, gastric and duodenal. Viloxazine plasma concentrations were low when administered by gastric and duodenal routes compared to those after intravenous injection. Concentrations to peak were 1-2 times higher after duodenal than gastric administration. Times to peak were 23.0 +/- 4.7 min after gastric administration and 9.5 +/- 5.4 min after duodenal administration. A better absorption of viloxazine after administration occurred in the duodenum than in the stomach; these results agree with viloxazine pKa = 8.13. The other pharmacokinetic parameters such as half-life, clearance and volume of distribution where the same irregardless of the administration route.

Administration, Oral↗

Effects of administration route on valproate pharmacokinetics in the rabbit.

The absorption of sodium valproate was studied in 5 rabbits. Each animal received the drug (70 mg/kg) via 3 routes: intravenous, gastric and duodenal. For the 2 extravascular routes, the absolute bioavailability F, maximal plasma concentrations Cmax, times to peak Tmax and absorption coefficients Kabs were the same. Absolute bioavailability was always close to unity. This indicated that valproic acid was absorbed from the intestine as well as from the whole gastrointestinal tract. The other pharmacokinetic parameters such as terminal plasma half-life, total clearance and volume of distribution remained unchanged whatever the route of administration.

Animals↗

Pharmacokinetics of lidocaine and bupivacaine in retrobulbar and facial block.

Analgesia can be obtained during ophthalmic surgery by regional anesthesia using local anesthetic agents. As in other indications, neurological complications may occur, especially because the site of injection is close to the central nervous system. In order to evaluate the risk of retrobulbar and facial block obtained after 40 mg lidocaine and 20 mg bupivacaine injection, pharmacokinetics of both drugs was evaluated in plasma obtained from 11 patients. In addition, 3 cerebrospinal fluid samples were analyzed. Maximal plasma concentration was 0.73 +/- 0.33 micrograms.ml-1 for lidocaine and 0.19 +/- 0.06 micrograms.ml-1 for bupivacaine, obtained 24.7 +/- 23.0 min and 12.0 +/- 3.7 min after the end of injection, respectively. CSF/plasma ratio was in the range 0.05-0.26 for lidocaine and 0.56-1.33 for bupivacaine. In all patients, regional anesthesia was sufficient to perform surgery without any other analgesic drug. No sign of cardiovascular or respiratory toxicity was observed during the study.

Adult↗

Comparative pharmacokinetic study of conventional and sustained-release viloxazine in normal volunteers.

Animal and human studies have indicated that viloxazine hydrochloride, an antidepressant drug with a half-life of 3-4 h in most subjects at low dosage, is rapidly and almost completely absorbed after oral administration. A sustained-release form might be useful to decrease the frequency of administration. In our study, the pharmacokinetics of sustained-release form containing 300 mg viloxazine were compared with 300 mg conventional viloxazine in 11 normal volunteers (6 women, 5 men). Wide interindividual variations were observed with respect to plasma levels, but there was no significant statistical correlation between weight and blood concentration (conventional form: Cmax = 3,599 +/- 579 ng/ml, tmax = 86 +/- 26 min; sustained-release form: Cmax = 1,917 +/- 922 ng/ml, tmax = 215 +/- 77 min). Twelve hours after administration, plasma levels ranged between 540 and 1,600 ng/ml for the conventional form and between 660 and 2,120 ng/ml for the sustained-release form. Despite the great interindividual variation this new viloxazine form appears to be of interest for one daily administration.

Administration, Oral↗

Effects of single oral doses of bromazepam, buspirone and clobazam on performance tasks and memory.

Three anxiolytic drugs (bromazepam 3 mg, buspirone 10 mg, and clobazam 10 mg p.o.) were evaluated for their effects on memory, psychomotor performance and subjective response in a double-blind, placebo-controlled, crossover study in 20 healthy volunteers. At each session, measurements were made before and 2 and 6 h after drug administration. The psychometric tests used were the images test, digit/symbol substitution test (DSST), choice reaction time (CRT), and critical fusion frequency (CFF). Free recall after 30 s in the 2-hour session was altered for all 3 drugs as compared to placebo (p less than 0.01), but in the 6-hour session only bromazepam showed a significant difference (p less than 0.05). The number of symbols reproduced by subjects during DSST was significantly decreased by bromazepam and buspirone as compared to placebo (p less than 0.05), whereas clobazam showed no differences with placebo. Analysis of variance for all four treatments (the 3 drugs and the placebo) showed no differences at recognition time or for motor response in CRT, except between bromazepam and clobazam after 6 h (p less than 0.05). None of the drugs altered performance during CFF (except bromazepam), and clobazam actually improved performance. All the drugs studied disturbed acquisition phenomena or restitution of memory; however, only bromazepam and buspirone significantly modified performance during DSST and disturbed the recognition and processing of sensory data.

Administration, Oral↗

Additive effects of clonidine and antidepressant drugs in the mouse forced-swimming test.

In the mouse forced-swimming model, dose-dependent reversal of immobility was induced by the alpha-agonist clonidine given IP 30 min before testing. In addition, three preferential inhibitors of 5-HT uptake (citalopram, indalpine and fluvoxamine) had similar activity in the dose range 8-16 mg/kg as did the 5-HT1 agonist 8-OH-DPAT (1-4 mg/kg). Pretreatment with alpha-methyl-paratyrosine (100 mg/kg) did not prevent clonidine (1 mg/kg) action, suggesting that there was mediation by alpha post-junctional receptors. The effect of clonidine was unaltered by prazosin (2 mg/kg) and reversed by yohimbine (4 mg/kg) and 5-MeODMT (1 mg/kg), whereas it was potentiated by reserpine (2.5 mg/kg), methysergide (2 mg/kg) and ketanserin (8 mg/kg). Moreover, an ineffective dose of clonidine (0.06 mg/kg at 45 min pre-testing) made active subthreshold doses of various antidepressants (given at 30 min pre-testing): imipramine (4 mg/kg), amitriptyline (1 mg/kg), maprotiline (8 mg/kg), citalopram (2 mg/kg), indalpine, fluvoxamine and mianserin (4 mg/kg), viloxazine (2 mg/kg). Similar interactions were found with iprindole and nialamide (32 mg/kg), which were inactive alone up to 64 mg/kg, and 8-OH-DPAT (0.5 mg/kg) but not with major and minor tranquillizers. It is suggested that one effect of antidepressants might be the triggering of different relationships between alpha-2 and 5-HT mechanisms.

Animals↗

Influence of alpha stimulants and beta blockers on yohimbine toxicity.

1. Potentiation of yohimbine-induced sublethality has been largely used to predict antidepressant action. 2. Several products were tested in order to understand the mechanism of this toxicity better: an alpha-1 central stimulant (adrafinil); an alpha-2 central stimulant (clonidine); and 4 beta-blockers (propranolol, atenolol, penbutolol and metoprolol). 3. It was found that atenolol and adrafinil could not antagonize toxicity, whereas clonidine and the other 3 beta-blockers could. 4. It is suggested that a central beta-origin toxicity exists since only beta-blockers which cross the blood-brain barrier are capable of antagonizing this activity. 5. The fact that clonidine also antagonized this toxicity may be explained by the beta-antagonist action of this substance at the high doses used.

Adrenergic alpha-Agonists↗

Pharmacokinetics and haemodynamic effects of prolonged methohexitone infusion.

1. The use of continuous infusion anaesthesia has only been of interest since the development of short-acting, less cumulative and less toxic drugs. 2. This study aimed to compare pharmacokinetics and haemodynamic effects during and after long time methohexitone constant rate infusion. Sixteen patients were given either 60 or 90 micrograms kg-1 min-1 methohexitone during 14 h. Blood samples were taken hourly during this time and 12 h following the end of infusion. 3. Infusion period was analysed by a single exponential model; post-infusion time showed a three compartment model, the intermediate phase parameters corresponding to those of the infusion period. 4. Methohexitone was haemodynamically well tolerated; prolonged infusion decreases oxygen consumption, mainly by a decrease in oxygen demand. 5. Many patients remained unconscious for unacceptably long periods of time after post-operative sedation by methohexitone.

Hemodynamics↗

Quantitative analysis of serum methohexital by GLC using capillary column and nitrogen-selective detection.

A gas chromatographic method for routine quantitation of methohexital in plasma samples is reported. One-step extraction in organic phase, the use of a fused silica capillary column, and nitrogen-selective detection permit simple, precise, and sensitive determination of methohexital in plasma. A linear relationship is described between peak height ratio and methohexital concentrations ranging from 0.125 to 50.0 micrograms/ml (r = 0.998). The sensitivity limit of the assay was 6 ng/ml in plasma. No interfering peak was observed with numerous other drugs. The procedure was successfully applied to the determination of pharmacokinetic parameters of methohexital after IV administration or continuous infusion in a child and an adult.

Chemical Phenomena↗

Effects of administration route on pharmacokinetics of aspirin in the rabbit.

The absorption of aspirin used in the form of lysine acetylsalicylate was studied in the rabbit. Each animal received the drug by three routes: intravenous, gastric and duodenal. Plasma concentrations of acetylsalicylic acid (ASA) and salicylic acid (SA) were compared. ASA plasma concentrations obtained after gastric or duodenal administration were low compared to those after intravenous injection. Concentrations were 2 to 5 times higher after gastric than duodenal administration. SA plasma concentrations were lower at the beginning of the experiment for gastric than for duodenal administration; after 90 min the concentrations were similar. A better absorption of aspirin (as lysine acetylsalicylate) after administration occurred in the stomach than in the duodenum, but the amount of ASA which reached the central compartment was quite poor.

Animals↗

Rapid gas-chromatographic assay of bupivacaine in plasma.

A method for estimating bupivacaine concentration in human plasma by capillary gas-chromatography using solid injection and nitrogen-specific detection is described. Etidocaine, another anilidetype local anesthetic was used as internal standard and added to the sample before single-step extraction with diethylether. This method demonstrates high sensitivity (6 ng/ml plasma) and combines selectivity, rapidity, and simplicity. Results of this procedure correlate well with those obtained by an HPLC method.

Bupivacaine↗