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J Lavarenne

Publications and source records attributed to J Lavarenne.

At least 19 recordsLinked to original sources
PubMed1992

High-performance liquid chromatographic determination of amitriptyline and its main metabolites using a silica column with reversed-phase eluent. Application in mice.

A method was developed for the assay of amitriptyline, amitriptyline N-oxide, nortriptyline, desmethylnortriptyline and E (trans) and Z (cis) isomers of 10-hydroxyamitriptyline and of 10-hydroxynortriptyline in plasma and brain of animals, using high-performance liquid chromatography with ultraviolet detection (254 nm). Single extraction was performed at pH 10.5 from 0.25 ml of plasma or 1 ml of brain mixture. Chromatographic separations were achieved with a silica column and an aqueous methanol mobile phase containing ammonia. This procedure offers high sensitivity (8-10 ng/ml), high linearity (r > 0.99) and acceptable precision (coefficient of variation < or = 13.3%). The method was used to determine levels of amitriptyline and its major metabolites in mice 30 min after a single intraperitoneal administration of amitriptyline (20 mg/kg).

Amitriptyline↗
PubMed1992

Comparative effects of different uptake inhibitor antidepressants in two pain tests in mice.

The purpose of this study was to compare the analgesic effect of acute injections (1.25 and 20 mg/kg, ip) of several antidepressants with different effects on monoamine reuptake, on two pain tests in mice (hot-plate and phenylbenzoquinone-induced abdominal writhes). Serotonergic inhibitors (citalopram, fluvoxamine and clomipramine) were more effective in the hot-plate test whereas noradrenaline reuptake inhibitors (desipramine and maprotilline) were more effective in the writhing test. The mixed antidepressants (amitriptyline and to a lesser degree trimipramine) were more effective in the two tests than the other antidepressant drugs. Changes in motor activity of clomipramine and amitriptyline could not account for the modifications of pain threshold. Amineptine (a dopamine reuptake inhibitor) failed to induce any antinociceptive effect in the hot-plate test and was hyperalgesic in the writhing test, which could be explained by an increased motor activity. These findings indicate that the antinociceptive potency of reuptake inhibitors varies according to their monoamine specificity and the nature of stimuli. They would suggest that the preferential choice of serotonergic antidepressants in the management of chronic pain is arguable.

Animals↗
PubMed1991

Evidence for a central but not a peripheral analgesic effect of clomipramine in rats.

The effect of clomipramine (CMI), a tricyclic antidepressant, was studied on an acute inflammatory pain model in an attempt to understand its potential antinociceptive activity, the involvement of a central and/or peripheral component and its influence on the inflammatory process. When administered (i.v.) before the inflammatory agent, carrageenan (CAR), CMI (0.125, 0.25 and 0.5 mg/kg) completely prevented the development of the hyperalgesia for 70-120 min according to the doses. This antinociceptive effect was suppressed by naloxone (100 micrograms/kg i.v.) for 65 min. Neither higher doses (1, 2 and 20 mg/kg, i.v.) nor CMI injected into the inflamed paw (15 min before CAR) modified pain thresholds. Moreover, CMI (0.5 and 2 mg/kg, i.v.) administered 15 min before CAR markedly increased the volume of the CAR-induced oedema. These results (1) demonstrate an opioid-dependent antinociceptive effect of CMI on this model, the doses used being lower than those active in thermal or electrical tests, and (2) tend to exclude a peripheral mechanism and an NSAID-like anti-inflammatory activity suggested by previous in vitro studies.

Analgesics↗
PubMed1988

Study of histamine release induced by acute administration of antitumor agents in dogs.

The effects of eight antitumoral drugs known to cause anaphylactoid side effects in clinical use were studied in dogs. Blood pressure, heart rate, and blood and plasma histamine levels were monitored. L-asparaginase, methotrexate, 5-fluorouracil, bleomycin, and cisplatin had no effect on these parameters. Doxorubicin, Vehem (teniposide), and Vepeside (etoposide) induced hypotension, tachycardia, and a rise in histamine levels. In the cases of Vehem and Vepeside, the excipient (respectively, cremophor EL and tween 80) induced the same effects. These agents, like elliptinium, which had been previously studied, induce nonspecific histamine release--unlike the other drugs studied. The mechanism of clinically observed anaphylactoid side effects is discussed in the light of these findings.

Anaphylaxis↗
PubMed1987

[Criteria for assessing granulocytic or platelet cytopenia caused by drugs. Results of consensus meetings].

The use of an official drug adverse reaction assessment procedure became compulsory in France in 1984. The method proposed various qualifications for the semiologic and chronologic criteria used to ascribe a disorder to a specific drug but did not define them. Consensus meetings have been organized in order to define, in the main pathological fields, the adverse reactions themselves and the various qualifications of the criteria. This paper reports the results of meetings attended by hematologists, members of the French national network of Pharmacovigilance and representatives of Roussel Uclaf Drug Monitoring Department for drug-induced granulocyte and platelet cytopenias. Participants studied (a) the limits of the time interval between the appearance of the adverse reaction and the beginning or the end of the treatment with the suspected drug; (b) interpretation of a possible rechallenge; and (c) diagnostic value of in vitro tests proposed to confirm the responsibility of a specific drug in a granulocytic or platelet cytopenia.

Agranulocytosis↗
PubMed1987

Benzodiazepine withdrawal seizures: analysis of 48 case reports.

Various reactions to benzodiazepine withdrawal have been widely described. Among these, seizures have occasionally occurred on abrupt withdrawal. Our own experience of 48 cases of seizures suspected to have been caused by benzodiazepine withdrawal and reported to the Adverse Drug Reaction (ADR) Monitoring Center (1979-1985) showed that a great variety of benzodiazepines with different half-lives were involved, those most frequently implicated being the most widely prescribed. The occurrence of seizures was not always related to the interruption of long-term treatment (from a few days to greater than 7 years) nor to high-dose treatment, the range of dosages being usually close to that recommended. However, in some cases, several benzodiazepines had been taken simultaneously. The time between the last intake of the drug(s) and the occurrence of the seizures was shorter when a short-life benzodiazepine had been used. Additional factors were frequently involved; these factors were present in 29 cases and were multiple in nine of them. The incidence of withdrawal seizures was related more to the presence of these additional factors than to either the pharmacokinetics of the drugs or the pattern of treatment.

Adult↗
PubMed1986

Acute hemodynamic effects of an antitumoral agent: elliptinium. Involvement of histamine release.

This work reports a study of cardiovascular effects of elliptinium, a recently-acquired antitumoral agent, acutely administered i.v. in the dog. Its hemodynamic effects (10 parameters) are detailed, and their mechanism of action is investigated by antagonist administration and determination of blood and plasma histamine levels. Elliptinium induces vasodilation and tachycardia. The former is mainly due to histamine release, and a brief and slight release of prostaglandins; the latter is due to a reflex to hypotension and release of catecholamines. These results agree with others using various compounds of the ellipticine family and anthracycline antitumoral agents. They suggest treatment to prevent anaphylactoid side effects observed with this drug in man and they raise the question of the usefulness, in antitumoral agent, of histamine releasing properties.

Alkaloids↗
PubMed1985

Cardiac and vascular effects of elliptinium in guinea pigs. Involvement of a histaminergic mechanism.

This work reports a study of the effects of elliptinium on heart rate, arterial blood pressure and capillary permeability in guinea-pigs. The variations in capillary permeability are determined by spectrophotometric assay of skin Evans blue. Elliptinium induces dose-independent tachycardia and dose-related hypotension. For the highest dose (6 mg/kg), elliptinium induces lethal collapse . Elliptinium increases capillary permeability and this effect, particularly marked at 1 mg, i.d., is partially antagonized by mepyramine-cimetidine association. These results are discussed in comparison with those obtained with elliptinium on other parameters, with histamine and with different antitumoral agents. The increase in capillary permeability raises the question of its relevance to the anticancer activity of elliptinium.

Alkaloids↗
PubMed1985

Use of experimental myocardial infarct to demonstrate arrhythmogenic activity of drugs.

Ligature of the anterior interventricular coronary artery in the dog is a model that is used, classically, to study antiarrhythmic properties of drugs. It can also be used to demonstrate arrhythmogenicity. In this study, twenty hours after coronary ligature, cardiac arrhythmia was reduced by oral administration of quinidine and phenytoin. This effect lasted over several days after the coronary occlusion. By Day 2, more than 60% of the treated dogs had a predominantly sinus heart rhythm, compared with 20% of the controls. This antiarrhythmic treatment also seemed to reduce mortality. Dipyridamole was subsequently injected i.v. at 0.5 and 1 mg/kg on Days 2, 3, and 4 after coronary ligature. On Day 2, dipyridamole significantly increased the proportion of ectopic beats and significantly lowered the proportion of sinus beats. This drug can thus worsen arrhythmia induced by coronary occlusion. On Days 3 and 4, dipyridamole showed no arrhythmogenic effects, but there was a significant increase in sinus automaticity.

Animals↗
PubMed1984

Bronchopulmonary effects of elliptinium in anesthetized dogs.

The bronchoconstrictor effect of elliptinium already demonstrated in the guinea-pig is shown in the dog. It is less intense and its onset is prompter. Successive administration of identical doses of elliptinium attenuates the bronchospasm induced, suggesting tachyphylaxis. The previously described indirect bronchoconstrictor effect involving endogenous mediators seems also to be active in these circumstances.

Alkaloids↗
PubMed1983

[Value of determining plasma INH during antitubercular treatment. Retrospective analysis of 204 cases].

The acetylator phenotype of 204 tuberculous patients was assessed (152 men and 52 women aged between 15 and 90). The INH dose was adjusted according to Vivien's protocol, measuring the index of inactivation of Isoniazid I3, three hours after the oral dose. In fixing the transition zone of I3 at 0.50 the distribution between slow and rapid acetylators was 53% and 47% respectively. There was no difference for sex, age or ethnic group. The dosage used according to this protocol varied greatly, going from 1.64 mg/kg/day to 13.3 mg/kg/day with a mean value of 2.74 mg/kg/day for slow acetylators and 6.13 mg/kg/day for rapid acetylators. The usual dose advised is 5 mg/kg/day, which may lead equally to over or under treatment though the former is more likely in our experience. Adjusting the dosage is an important feature in good tolerance of the treatment: indeed only 4 of 86 subjects whose dosage has been adjusted showed elevated transaminases, whereas 34 of 118 patients had raised transaminases in the control group on a standard dose before the adjusted treatment was introduced. The difference was significant between the two groups.

Acetylation↗
PubMed1982

[Drug interactions with macrolids compared action of two macrolids on liver microsomal activity ].

Pharmacokinetic parameters for elimination of antipyrine, regarded as a marker of the oxidative activity of liver microsomes, were studied in six health volunteers after oral administration of 1 g of the drug. Elimination half life and metabolic clearance were determined prior to (controls) and on day 2 of a treatment with troleandomycin (1500 mg/day), on days 7 and 14 of a treatment with midecamycin (1200 mg/day) and on days 7 and 14 of a treatment with phenobarbital (100 mg/day) as reference. A marked difference was evident between troleandomycin (whose inhibitor effects on the liver metabolism of certain drugs (ergot derivatives, theophylline, etc) are known, and midecamycin. This one had no inhibitor action and this finding is consistent with previous results bearing on the pharmacokinetics of theophylline during antibiotic therapy: only on the 14th day was a slight inductor effect seen, but it remained much lower than that of phenobarbital whose effects were significant on both the 7th and the 14th days.

Adult↗