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Biomedical subjects

S Vandel

Publications and source records attributed to S Vandel.

At least 55 records · Page 3Linked to original sources
PubMed1982

Relationship between the plasma concentration of clomipramine and desmethylclomipramine in depressive patients and the clinical response.

Thirty one in-patients suffering from depression were treated orally with clomipramine (C1) at various dosage, for 28 days, after a "wash-out" period of three days. In 17 patients receiving 75 mg per day of C1, steady state plasma levels of C1 were reached at Day 14, and steady state plasma levels of its active metabolite, desmethylclomipramine (DMC1), were reached at Day 21. In contrast, in 7 other patients receiving a dosage increasing to 150 mg per day at Day 7, mean plasma levels of C1 and DMC1 continued to rise during the entire treatment period. At the steady state, a correlation was found between C1 dosage expressed as mg kg body weight and the plasma concentration of C1 and DMC1. Factors such as tobacco and alcohol consumption seem to modify the C1/DMC1 ratio. A comparison of clinical response with plasma levels of C1, DMC1 and C1 + DMC1 showed a significant negative linear correlation.

Adult↗
PubMed1981

Clinical pharmacology of viloxazine hydrochloride.

Plasma concentrations of viloxazine were determined in twenty depressed inpatients during 4 weeks of treatment with progressively increasing dosage. Viloxazine plasma levels varied markedly during the day, due to the short half-life of the drug. Plasma levels rose to peak values after 7-10 days of treatment and then decreased, perhaps due to enzymatic induction by viloxazine. A negative linear correlation was found between the plasma concentration of viloxazine and its clinical effect, with the best clinical improvement in patients whose plasma concentration was 20-500 ng/ml at 7 a.m. Performance in psychomotor tests (visual reaction time and ring of Pierron was improved in many patients after treatment and was correlated with the plasma viloxazine level and the Hamilton Rating score. Assessment of viloxazine effects of electroencephalogram showed a decrease in EEG amplitude in the eight clinically improved patients.

Depressive Disorder↗
PubMed1981

[Clomipramine and desmethylclomipramine: relationship between plasma levels and clinical effect (author's transl)].

Pharmacokinetic can perhaps explain that about 30% of depressed patients do not respond to tricyclic antidepressants. Studies of the relationship between the pharmacokinetic and pharmacological effects of the tricyclic antidepressants are particularly important. Clomipramine is a tricyclic antidepressant widely used. But there are disparities in various findings on relationship between plasma levels of this drug and clinical effect. Forty in-patients, with an endogenous or exogenous depressive syndrome, received clomipramine orally. In 19 patients treated by 75 mg per day of clomipramine, there was a great interindividual variability of the plasma levels at the 28 day treatment. A comparison of clinical response with plasma levels of clomipramine and desmethylclomipramine, showed a significant negative linear correlation at day 28.

Adjustment Disorders↗
PubMed1978

Clinical response and plasma concentration of amitriptyline and its metabolite nortriptyline.

Plasma levels of amitriptyline and nortriptyline were measured twice weekly in 62 patients treated for three weeks with i.m. amitriptyline 120 mg/day. In half the patients the ratio of amitriptyline to nortriptyline was under 1 and in the other half it was greater than 1. 30 of these 62 patients were clinically monitored with the Hamilton Rating Scale and the side effects of the drug were recorded. There was no correlation between plasma level of the drug and its side effects, but there was a statistically significant curvilinear correlation between the plasma levels of amitriptyline plus nortriptyline and nortriptyline alone, and the clinical effect. The practical value of this type of investigation was demonstrated by showing that patients whose drug plasma level was not in the therapeutic range, were clinically improved after adjustment of the dose. The plasma level of amitriptyline plus nortriptyline must lie between 60 to 220 ng/ml, and that of nortriptyline between 60 to 140 ng/ml, to obtain the best clinical effect. Associated treatments, age, weight and sex of patients, and the type of depression did not appear significantly to affect the plasma level of the drug.

Adult↗
PubMedDate not supplied

Pharmacokinetics of viloxazine hydrochloride in man.

The pharmacokinetic characteristics of a new antidepressant, viloxazine hydrochloride, were investigated in five males and five females to study sex differences. Plasma levels were determined over a period of 9 h after a single dose of viloxazine of 100 mg (expressed as base). The half life of the drug was in the range of 2.19 - 4.21 for females and 2.61 - 4.31 h for males. The maximum plasma levels occurred in 29 - 171 min of the oral dose for females and 54 - 155 min for males. They reached 1382 - 1769 ng/ml-l for females and 1108 - 2932 ng/ml for males. Pharmacokinetic data were not statistically different between males and females.

Adult↗
PubMedDate not supplied

[Grapefruit juice as a contraindication? An approach in psychiatry].

The authors investigated in this preliminary study the influence of grapefruit juice on the metabolism of two tricyclic antidepressants. An increase of plasma concentrations is observed indeed for many drugs when administered concomitantly with grapefruit juice. This effect was mainly attributed to inhibition of cytochrome P450 1A2 and 3A4 enzymes by naringenin. These isoenzymes are involved too in the metabolism of many psychotropic drugs. Only two benzodiazepines (midazolam and triazolam) were studied in the conditions of grapefruit juice association. All these studies are performed in healthy subjects and with a study design very different from the clinical conditions. On the basis of these considerations, the authors hypothesized that grapefruit juice should inhibit tricyclic antidepressant metabolism and thus increase the bioavailability of these drugs. They want to precise if this possible drug plasma level increase could be clinically important for depressed patients. Fourteen depressed inpatients were selected for the study. Seven of them received amitriptyline (100 to 150 mg/d) and the seven others clomipramine (112.5 to 225 mg/d). Tricyclic antidepressant and desmethylated metabolite plasma levels were determined on four occasions. The first and second day samples were obtained to determined the plasma level intraindividual variability of antidepressants. On the third and fourth days, plasma levels were determined after an oral coadministration of the antidepressant and 250 ml of pure and fresh grapefruit juice. One patient was excluded from the study due to the coadministration of clomipramine and fluvoxamine. There is indeed a major drug-interaction between these two drugs, and the tricyclic antidepressant plasma levels of this patient were in the toxic range, without side effect. In this group of patients, there was no metabolic interaction between amitriptyline and grapefruit juice. But the mean plasma levels of clomipramine and desmethylclomipramine increased after coadministration of this juice (+4.5% and +10.5% respectively). The authors concluded that with these preliminary results, the potential clinical relevance of this interaction cannot be estimated.

Adult↗
PubMedDate not supplied

[Clinical tolerance of a new antidepressant -- milnacipran].

Milnacipran is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake with a good safety and tolerability profile. The efficacy and tolerance profile of this antidepressant have been compared with those of tricyclic and selective serotonin reuptake inhibitor antidepressants (SSRIs) in open-label and placebo-controlled trials. But no data in clinical practice are available. The authors studied the tolerability of milnacipran (100 to 200 mg/d) in 28 depressed inpatients receiving usual comedications during a mean period of 33 days (3 to 107 days). The incidence of adverse events was determined with the help of the Pharmacovigilance Center of the Centre Hospitalo-Universitaire (Besançon, France). Among the 28 patients, milnacipran was well tolerated by 18 of them. Side-effects were noted in 10 patients, but they led to withdrawal of the antidepressant in only 2 cases, where dyspnea, palpitations, pollakiuria in a case and headache, nausea, dysuria in the other case occurred. The most frequent adverse event observed was hypotension (n = 6), but in each case it occurred just after the addition of sedative phenothiazines (n = 5) or of a comedication with phenothiazines and valpromide (n = 1). So this side-effect could not be attributed to milnacipran alone. Treatments with heptaminol or theodrenaline and cafedrine were useful. An increase of the cardiac frequency seemed to occur with milnacipran (p < 0.06). It was observed in the 5 inpatients for whom this cardiovascular parameter was recorded before and during the milnacipran treatment. In 5 other patients, the cardiac frequency seemed to decrease when milnacipran was stopped for lack of good efficacy or adverse events. Gastrointestinal disturbances were scarce isolated (nausea n = 1), but necessitated a treatment with metopimazine. The milnacipran prescription (100 mg/d) after an other antidepressant treatment had been done without a withdrawal period and without problem, even when the previous antidepressant was a SSRIs with a long half-life and CYP450 inhibitory properties. The authors concluded to the good tolerability of milnacipran in usual clinical practice.

Adult↗
PubMedDate not supplied

[Extrapyramidal side effects of neuroleptic and antidepressant treatment: assessment of potential risk factors through CYP2D6 genetic polymorphism].

The objective of this study was to assign metabolizer phenotype (cytochrome P450 2D6 or CYP2D6) to drug treated psychiatric adult patients to assess if the CYP2D6 polymorphism could be a potential risk factor for the development of extrapyramidal side effects of psychotropic drugs. Twenty-eight unrelated in-patients (16 men and 12 women) treated with antidepressants and/or antipsychotic drug were phenotyped using dextromethorphan. Two groups of patients were considered depending on the presence (n = 14) or not (n = 14) of extrapyramidal side effects. The mean dextromethorphan/dextrorphan metabolic ratio (log10) did not differ between the two groups of patients (-1.13 +/- 0.9 and -1.56 +/- 0.5, NS). But significantly more patients with extrapyramidal side effects (n = 4) than patients without side effects (n = 0) were poor metabolizers. This result could be due to a quantitative difference between the 2 groups of drug treatment cosegregated with dextromethorphan, but several authors reported that extrapyramidal side effects seemed not to be always related to high plasma drug levels. So the authors concluded that the 2D6 polymorphism could be a risk factor of poor neurologic tolerance of psychotropic drugs, but not only through pharmacokinetic consequences. CYP 2D6 is indeed expressed in brain and seems to interfer with the metabolism of dopamine and other related neurotransmitters.

Adolescent↗
PubMedDate not supplied

Drug extrapyramidal side-effects or not: is there a dextromethorphan phenotype difference?

A recent hypothesis suggests the possible role of cytochrome P450 2D6 (CYP2D6) polymorphism (involved in the metabolism of a large number of drugs), as a potential risk factor for the development of extrapyramidal side-effects of psychotropic drugs. The CYP2D6 metabolizer phenotype (dextromethorphan test) of 31 drug treated psychiatric adult patients suffering from extrapyramidal side-effects (group 1) and of 31 matched patients without drug side effects (group 2) were compared. In the first group, 13 poor metabolizer patients (41.9 per cent) were found, characterized by a dextromethorphan metabolic ratio > 0.3, and only two patients in the second group (6.4 per cent). These data provide some support for the notion that in subjects in whom CYP2D6 is probably saturated, the risk of drug extrapyramidal side-effects may be increased. In such patients the choice of psychotropic drugs 'without' this risk must be preferred.

Adolescent↗