Psychological stress and cortisol secretion in anhedonic alcoholic men.

We investigated plasma cortisol in a psychological stress paradigm in seven weaned anhedonic alcoholics in comparison with seven age-matched healthy controls. Alcoholics had significantly higher mean plasma cortisol at baseline and no increase following a psychological stress paradigm. Anhedonic alcoholics judged the experimental situation less agreeable than controls. Anhedonic alcoholics may have blunted cortisol response to psychological stress.

Sensitive determination of nefopam and its metabolite desmethyl-nefopam in human biological fluids by HPLC.

Nefopam (NEF) and desmethyl-nefopam (DMN) were assayed simultaneously in plasma, globule and urine samples using imipramine as internal standard. A liquid-liquid extraction procedure was coupled with a reverse phase high-performance liquid chromatography system. This system requires a mobile phase containing buffer (15 mM KH(2)PO(4) with 5 mM octane sulfonic acid: pH 3.7) and acetonitrile (77:33, v/v) through (flow rate=1.5 ml/min) a C(18) Symmetry column (150x4.6 I.D., 5 micrometer particle size: Waters) and a UV detector set at 210 nm. Internal standard was added to 1 ml of plasma or globule sample or 0.5 ml of urine sample, prior to the extraction under alkaline ambiance with n-hexane. The limits of quantification were 1 and 2 ng/ml for both molecules in plasma and globule, respectively; 5 and 10 ng/ml for NEF and DMN in urine, respectively. The method proved to be accurate and precise: the relative error at three concentrations ranged from -13.0 to +12.3% of the nominal concentration for all molecule and biological fluid; the within-day and between-day precision (relative standard deviation %) ranged from 1.0 to 10.1% for all the molecules and biological fluids. The method was linear between 1 and 60 ng/ml for both molecules in the plasma; 2 and 25 ng/ml for both molecules in the globule; 25 and 250 ng/ml for NEF and 50 and 500 ng/ml for DMN in the urine: correlation coefficients of calibration curves (determined by least-squares regression) of each molecule were higher than 0.992 whatever the biological fluid and during the pre-study and in-study validations. This method was successfully applied to a bio-availability study of NEF in healthy subjects.

Pharmacodynamics and pharmacokinetics of single nasal (5 mg and 10 mg) and oral (50 mg) doses of ephedrine in healthy subjects.

OBJECTIVE: To determine the cardiovascular, subjective effects and potential of abuse liability of single dose (-) ephedrine (E) administered orally (50 mg) or intranasally (10 mg and 5 mg). METHODS: Sixteen healthy Caucasian men with no history of drug/alcohol/nicotine abuse or dependence received intranasal single doses of E 5 mg, 10 mg and oral doses of 50 mg and placebo in a double-blind, double-dummy, crossover study. Dependent measures included assessment of subjective feelings by Addiction Research Centre Inventory (ARCI). Profile of Mood States (POMS). visual analogue scales (VAS); "drug liking", "any drug effect", subjective quality of sleep and blood pressure and heart rate. Plasma E concentrations were also determined. RESULTS: (-) E increased supine systolic, diastolic blood pressure (P < 0.01). Changes in supine systolic blood pressure (areas under the 8 h of the experimental sessions) were -59 +/- 47 mmHgh with placebo, -59 +/- 57 mmHg-h with E5 mg by the nasal route, -18 +/- 48 mmHg x h with E 10 mg by the nasal route and 13 +/- 58 mmHgh with E 50 mg by the oral route (P<0.001). (-) E-induced orthostatic hypotension (P < 0.01) (maximal systolic blood pressure drop: E 50 mg 14 +/- 10 mmHg, P < 0.03; E 10 mg 11 +/- 6 mmHg, P = 0.08 compared with placebo) and resulted in decreased tiredness (placebo -2 +/- 39 mm x h, E 5 mg -17 +/- 39 mm x h, E 10 mg -30 +/- 42 mm x h, E 50 mg -24 +/- 35 mm x h; P < 0.03). E did not modify ARCI subscales--in particular the "amphetamine" subscale--but showed a tendency for drug liking (P= 0.09). On the "any drug effect" questionnaire, subjects could identify drug effect (P=0.007). Maximal plasma E concentration (Cmax) and areas under the curves for up to 8 h were proportional to the doses. Elimination half-life was approximately 6 h. A clockwise hysteresis was observed for systolic blood pressure in all but one subject with E 50 mg by the oral route. CONCLUSION: E even at low doses and by the nasal route can decrease tiredness in healthy persons; this is accompanied by a substantial increase in blood pressure and orthostatic hypotension exposing individuals in case of intensive physical exercise to cardiovascular risks. No clear evidence of abuse liability in healthy drug naive subjects was observed.

Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects.

AIMS: Itraconazole is a potent inhibitor of CYP3A4 activity and is often used in combination with corticosteroids. Since the latter are partly metabolized by CYP3A4, we studied the interaction between itraconazole, prednisone and methylprednisolone in healthy male subjects. METHODS: The effects of 4 days administration of oral itraconazole (400 mg on the first day then 200 mg day-1 for 3 days) on the pharmacokinetics of prednisolone after a single oral dose of prednisone (60 mg) and the pharmacokinetics of methylprednisolone after single oral dose of methylprednisolone (48 mg) were studied in 14 healthy male subjects in a two-period cross-over trial. Plasma cortisol concentrations were determined as a pharmacodynamic index. RESULTS: Itraconazole increased the mean area under the methylprednisolone concentration-time curve from 2773 ng ml-1 h to 7011 ng ml-1 h (P < 0.001) and the elimination half-life from 3.2 h to 5.5 h (P < 0.001). The pharmacokinetics of prednisolone were unchanged. Cortisol concentrations at 24 h were lower after administration of methylprednisolone with itraconazole than after methylprednisolone alone (24 ng ml-1 vs 109 ng ml-1, P < 0.001). CONCLUSIONS: Itraconazole increased methylprednisolone concentrations markedly with enhanced suppression of endogenous cortisol secretion, but had no effect on prednisolone pharmacokinetics. The pharmacokinetic interaction between methylprednisolone and itraconazole is probably related to inhibition of hepatic CYP3A4 activity by itraconazole.

Sensitive determination of ephedrine and norephedrine in human plasma samples using derivatization with 9-fluorenylmethyl chloroformate and liquid chromatography.

A high-performance liquid chromatography procedure for the determination of ephedrine and norephedrine using fluorimetric detection in plasma samples is described. A double liquid-liquid extraction was performed, followed by derivatization with 9-fluorenylmethyl chloroformate. The extracts were chromatographed with a 5-microm C18 (150x4.6 mm I.D.) column using a mobile phase composed of acetonitrile and water (52:48; v/v). The excitation and emission wavelengths were respectively 264 nm and 313 nm. Calibration curves were linear over the range 0 to 300 ng/ml for each analyte. The specificity of the method was demonstrated with several FMOC-reacting drugs. The limits of quantification are similar to those obtained with the reference method: 2 ng/ml for ephedrine and 5 ng/ml for norephedrine. This method has been successfully applied to the determination of ephedrine and norephedrine plasma levels after administration of low doses of ephedrine to healthy subjects.

Beraprost sodium-fluindione combination in healthy subjects: pharmacokinetic and pharmacodynamic aspects.

Beraprost sodium (BPS), an orally active PGI2 (prostaglandine 12) analogue possesses vasodilatating and platelet aggregation inhibiting properties. It is being developed in peripheral arterial occlusive disease. As in future clinical practice BPS might be co-prescribed with oral anticoagulants, we investigated its interaction with fluindione, a vitamin K antagonist in healthy subjects in a randomised, double-blind, placebo-controlled, crossover study. Twelve healthy Caucasian male subjects randomly received BPS 40 microg t.i.d. or placebo for 3 days. There was a 7 day wash out between the two treatment periods. On day 3 of each treatment, the subjects ingested concomitantly a single oral dose of 20 mg of fluindione. The main assessment criterion was fluindione's pharmacokinetics. Secondarily, pharmacodynamic measurements of coagulation (prothrombin time, and International Normalised Ratio, INR) and platelet function (in vitro closure time assessed by PFA-100) were performed. Fluindione was assayed by HPLC with UV detection up to 96 h post-drug. No statistical difference could be evidenced on any fluindione pharmacokinetic parameters between BPS and placebo phases: t 1/2 (h): 35.9 (8.2) vs. 34.0 (4.2) [90% CI 105.8 (95.5-116.2)]; T(max) (h): 2.0 (0.5-6.0) vs. 4.0 (0.5-6.0) [90% CI 136.4 (70.7-208.9)]; Cmax (mg/L): 3.1 (0.6) vs. 2.9 (0.5) [90% CI 94.1 (85.8-103.2)]; AUC 0-inf (mg/h/L): 117.0 (31.5) vs. 113.9 (33.8) [90% CI 97.6 (87.5-108.8)]. The studied doses of BPS did not affect platelet function, at least as assessed by the in vitro platelet function testing. Twenty milligrams of fluindione marginally modified the PT ratio and INR, however, no statistically significant difference was found between BPS and placebo phases. In conclusion, a 3 day regimen of BPS 40 microg t.i.d. by oral route does not seem to affect pharmacokinetic parameters of a fluindione 20 mg single dose.

Anhedonia and relapse in alcoholism.

The aim of this study was to determine the role of anhedonia among other psychopathological dimensions in the relapse of alcoholics 6 months after withdrawal. Psychometric assessments included: the Social and Physical Anhedonia Scales, the Sensation Seeking Scale, the Pleasure-Displeasure Scale (including Fawcett-Clark's Pleasure Scale), the Depressive Mood Scale, the Thymasthenic Syndrome Rating Scale and the Comprehensive Psychopathological Rating Scale. Forty-four alcoholics participated in the study. The baseline values recorded during the second week of treatment showed that the more anhedonic the alcoholics were, the less they sought sensations. Type 2 alcoholics (Cloninger's classification) scored higher on the Thrill and Adventure Seeking Subscale. Relapsed alcoholics had higher baseline values on the Thrill and Adventure Seeking Subscale. This was in agreement with the step-wise discriminant analysis which showed that this subscale was the main variable that differentiated abstinent alcoholics from those who relapsed. Our results indicate that anhedonia does not predict relapse.

Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects.

OBJECTIVES: To assess whether acute 5-hydroxytryptamine-1A (5-HT1A)-receptor-mediated corticotropin, cortisol, and temperature responses are maintained after 3 weeks of treatment with controlled-release (CR) ipsapirone and fluoxetine compared with placebo and whether changes are reversible after cessation of treatment. METHODS: This was a randomized parallel-group study. Ten healthy subjects received ipsapirone CR or fluoxetine, and eight received placebo in a double-blind manner. An ipsapirone challenge test with 20 mg ipsapirone immediate-release formulation (IR) was performed before treatment (day 0) and after 20 days of treatment with placebo, 80 mg/day ipsapirone CR, or 20 mg/day fluoxetine (day 21). From day 22 to day 34 all subjects received placebo in a simple-blind manner. A third ipsapirone challenge test was performed on day 35. RESULTS: Before treatment, resting plasma corticotropin and cortisol concentrations and increases in plasma corticotropin and cortisol concentrations after challenge with 20 mg ipsapirone IR were similar for the three groups. After 20 days of treatment, plasma corticotropin and cortisol concentrations were similar before challenge, but ipsapirone IR-induced increases in plasma corticotropin and cortisol concentrations were significantly lower in both the ipsapirone CR group (corticotropin, 6.5 +/- 2 pg/ml; cortisol, 1.5 +/- 0.7 micrograms/dl) and fluoxetine group (corticotropin 4.4 +/- 2 pg/ml; cortisol 1.5 +/- 0.7 micrograms/dl) compared with placebo (corticotropin, 34 +/- 14 pg/ml; cortisol, 5.8 +/- 2 micrograms/dl, mean +/- SEM). After 2 weeks of placebo administration, plasma corticotropin and cortisol responses to ipsapirone IR again became identical in all three groups. Plasma ipsapirone concentrations were similar in all groups during each challenge. The hypothermic response to ipsapirone IR showed no difference before treatment, at the end of the treatment period, or 2 weeks after cessation of treatment. Long-term administration of antidepressants to the healthy subjects did not lead to any serious adverse effects. CONCLUSIONS: Long-term administration of fluoxetine and ipsapirone did not influence resting plasma corticotropin and cortisol concentrations in the morning. Stimulation of corticotropin and cortisol release by a selective 5-HT1A-agonist is reduced with long-term administration of these serotoninergic antidepressants. This subsensitivity of postsynaptic 5-HT1A-receptors is reversible.

Sensitivity and specificity to amphetamine of a French version of the 49-item form of the addiction research center inventory.

The main metrological characteristics of a French version of the 49-item addiction research center inventory (ARCI) were evaluated using data collected in three controlled studies in healthy subjects. An analysis of variance showed no study effect, so the three studies were pooled. The test-retest reliability coefficients after placebo evaluated by a Spearman rank correlation test were 0.64 (P < 0.0001) for subscale A, 0.49 (P < 0.0001) for subscale BG, 0.55 (P < 0.0001) for MBG, 0.58 (P < 0.0001) for PCAG and 0.27 for LSD (not significant). Using the same test, the test-retest reliability coefficients after amphetamine were 0.73 (P < 0.0001) for subscale A, 0.61 (P < 0.0001) for subscale BG, 0.71 (P < 0.0001) for MBG, 0.46 (P < 0.0001) for PCAG and 0.66 for LSD (P < 0.0001). In order to assess the predictive validity of the translated questionnaire, areas under curves were calculated from the ROC diagrams for the three scores, amphetamine (A), benzedrine group (BG) and morphine benzedrine group (MBG). Two criteria validity were used: the desire to take amphetamine another time and the discrimination of the allocated treatment (amphetamine or placebo). The calculated areas under curves indicated a good capacity of prediction of the three ARCI subscales (A, BG, MBG) for both criteria.

Effects of befloxatone, a reversible selective monoamine oxidase-A inhibitor, on psychomotor function and memory in healthy subjects.

Befloxatone is a new reversible and selective monoamine oxidase (MAO-A) inhibitor that has been shown to have antidepressant activity in various animal models. To assess the effects of single oral doses of befloxatone (5, 10, and 20 mg) on psychomotor performance and memory, a randomized, double-blind, five-way, crossover study with both placebo and amitriptyline (50 mg) was carried out in 15 healthy male volunteers. Psychomotor and cognitive functions were evaluated using both objective measures, including Critical Flicker Frequency (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Test (DSST), and a picture memory test and subjective measures, including Visual Analog Scales (VAS) and Addiction Research Center Inventory (ARCI), before and 2, 4, and 8 hours after administration. Pupil diameter was recorded by videopupillography. Single doses of befloxatone from 5 to 20 mg did not result in any detrimental effects on skilled performance and memory. In contrast, amitriptyline significantly impaired arousal (CFF), speed of reaction (CRT), information processing (DSST) and long-term memory (delayed free recall of pictures) and produced subjective sedation from 2 to 8 hours after administration. At the doses studied amitriptyline induced miosis but befloxatone did not modify pupil diameter. There was no evidence in this study to suggest that befloxatone, at the doses studied, has any sedative or amnesic effects in healthy subjects.

[Addictive potential in man: methodological aspects]. / Potentiel addictif chez l'homme: aspects méthodologiques.

Different methods have been developed in clinical abuse liability testing in man. Tolerance, psychic and/or physical dependence must be investigated through clinical studies during drug development of a new substance. Adequate methodology is needed using double-blind, time-blind evaluations, comparisons of different dose levels and duration of treatment for a given drug, abrupt and gradual interruption of treatment, appropriate period of observation after treatment cessation ... The optimal scale to evaluate properly the symptoms occurring after drug discontinuation is still under investigation. These studies will or should permit the differentiation of rebound, withdrawal and recurrence. Methods developed to study reinforcing effects in post-addicts and healthy subjects are self-administration and choice procedures. In addition, the more traditional approach has been through assessing self-reported effects in which standardized questionnaires are used (Addiction Research Center Inventory or A.R.C.I.; Single Dose Questionnaire or S.D.Q.). A third focus of measurement has been discrimination studies performed in individuals with histories of drug abuse as well as healthy subjects. Abuse-liability testing of a new compound needs a multidimensional assessment to optimize the predictivity in defining the relative risk.

Single dose of prednisone does not induce amphetamine-like subjective effects in healthy subjects.

Among the methods developed in assessing abuse liability, the behavioural and subjective effects of drugs can be recorded using the Addiction Research Center Inventory (ARCI) in drug-experienced subjects and normal volunteers. Sixteen healthy volunteers with no history of drug abuse participated in the study. The subjective, behavioural and physiological effects of prednisone (30 and 60 mg) were compared with those of dextroamphetamine (15 mg) and placebo in a randomized double-blind Latin square design. The self-questionnaires (ARCI, Profile of Mood States, Visual Analogue Scales and Sleep Questionnaire) were completed before, 1, 2, 4 and 8 h post single oral dosing. Results showed that subjective effects of the two studied doses of prednisone did not resemble those induced by dextroamphetamine (15 mg). These results indicate that oral single doses of prednisone do not possess amphetamine-like subjective effects in a healthy population. The well established psychostimulant effect of amphetamine have been replicated on almost all subjective assessments.

Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist.

The possible effects on memory, psychomotor performance and mood of eliprodil, a new non-competitive NMDA receptor antagonist acting through the polyamine modulatory site, was assessed in a randomized, double-blind, cross-over, placebo-controlled study involving 11 healthy young male volunteers. Eliprodil 30 mg, a placebo and midazolam 15 mg, a positive control, were administered as a single oral dose at 1 week wash-out intervals. Objective tests evaluated both memory (Sternberg memory scanning and paired words for short-term memory, delayed free recall of pictures for long-term memory) and psychomotor functions and arousal (critical flicker fusion threshold, choice reaction time, body sway). Mood was assessed using self-ratings (LARS, POMS, ARCI). Statistical analysis was performed using an ANOVA with pairwise comparisons using Tukey's method. A single dose of eliprodil 30 mg was free of any detrimental effect on memory and skilled performance and did not produce either subjective sedation or excitation or psychotomimetic effects in comparison with placebo. In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory). The potent sedative activity of midazolam, peaking 1 to 3 h post-dose, was confirmed by subjective evaluation and had disappeared 8 h post-dose.

The pharmacokinetics and electrocardiographic effects of chloroquine in healthy subjects.

Chloroquine prophylaxis was administered to 3 healthy male volunteers at 100 mg base/day for 25 days, followed by the curative dose at 25 mg base/kg for 3 days. Subjects attained effective chloroquine (mean = 50 micrograms/l) and desethylchloroquine (mean = 17 micrograms/l) concentrations by the 3rd week of prophylaxis, underlining the need to start chloroquine prophylaxis two weeks before travel. On the second day of the treatment period, hourly electrocardiographic monitoring showed a diminution of the T wave and prolongation of the QTc interval, manifesting cumulatively during the 3 days' curative dose, but with no cardiac symptoms. A dose-dependent cumulative effect of chloroquine was demonstrated with higher blood concentrations during the treatment period. Electrocardiographic readings spontaneously normalized after the treatment period as drug concentrations diminished progressively.

Cognitive impairments induced by triazolam in healthy volunteers: antagonism by a partial inverse agonist of benzodiazepine receptor.

Pharmacological studies revealed that SR 25776 possesses marked stimulant activity characteristic of a partial inverse agonist of benzodiazepine receptor. The effects of SR 25776 500 mg alone and in combination with triazolam 0.25 mg on psychomotor performance and memory were assessed in 8 healthy consenting male volunteers in a double-blind placebo controlled trial. Treatment effects were monitored before and two and half hours following oral medication. The present study suggest that at the studied dose SR 25776 may incompletely antagonize the sedative and amnesic effects of a benzodiazepine agonist without producing marked effects of its own.

[Value of autoquestionnaires in the evaluation of sex disorders related to drugs]. / Intérêt des autoquestionnaires dans l'évaluation des troubles sexuels liés aux médicaments.

Symptoms can be assessed by the subject or the patient himself. Drug-related sexual dysfunction may be of clinical relevance for medication compliance. Three kinds of self-rating scales are available: yes/no questionnaire, multiple choice questionnaire and visual analogue scales. Self-rating can be absolute (intensity score) or relative (improving or worsening score), over last rating or over baseline. Self-rating necessarily implies: comprehension of the vocabulary and the instructions by the subject; cooperation of the subject; and careful checking of the answers by the clinician. Main metrologic qualities are sensitivity, reliability and validity. To assess changes in sexual function, the "golden" sexual function questionnaire does not seem to exist. Separate questionnaires are provided for men and women with appropriate changes for specific items. The number of questions varies from 4 to 20 even more. Several aspects of the male and female sexuality must be studied. Two main questions can be raised: 1) is there any relation between responses obtained with self-reported questionnaire and responses to questioning by a clinician? is there any relation between self-reported sexual dysfunction and objective measures of sexual function like plethysmography?

Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects.

Zolpidem is a rapid-onset, short-duration imidazopyridine hypnotic drug and is specific agonist of the omega-1 (BZD1) receptors. Its hypnotic characteristics resemble those of triazolam. The aims of this study were to assess the effects of zolpidem on memory (the main objective), psychomotor performances, and postural sway (secondary objectives) in 18 healthy subjects and to compare them with those of triazolam and placebo. Short- and long-term memory (paired words associate and pictures test), psychomotor performances (critical flicker fusion frequency, choice reaction time, digit symbol substitution test), and postural sway were evaluated before and 1.5, 4, 6, and 8 h after the administration of a single dose of zolpidem (10 mg), triazolam (0.25 mg), and placebo. For each assessment, the maximal effect for both hypnotic drugs occurred 1.5 hour after intake. Both drugs decreased psychomotor performance, impaired memory, and increased postural sway. The effects of both hypnotic agents were short lasting, and no alterations were found 6 and 8 hours, respectively, after drug intake. No clinically relevant differences were found between zolpidem and triazolam for memory, psychomotor performance, postural sway, or adverse effects. It may be concluded that zolpidem, like triazolam, impairs short- and long-term memory, psychomotor performances, and postural sway and that these effects are of short duration.

Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses.

The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.

[Pharmacology of the memory. Review of cognition activator pharmacology]. / Pharmacologie de la mémoire. Revue de la pharmacologie des activateurs cognitifs.

The pharmacology of memory is fraught with problems. For one thing, the lack of consensus on the definition of memory and the absence of reference compound create clinical validation problems for new drugs. Then, it is difficult to predict clinical effectiveness on the basis of animal experiments and data obtained from healthy subjects, and this is due to the lack of analogy between animal models and clinical situations. Finally, to this must be added the complexity and variety of the possible modes of action of the agents under study. Thus, the pharmacology of cognition activators is closely dependent upon both fundamental research and clinical research.

[Drug evaluation in healthy volunteers. Legislative and ethical aspects]. / Les essais de médicaments chez le volontaire sain. Quelques aspects législatifs et éthiques.

Studies in healthy volunteers have been legalized since December 20th 1988 in France. The healthy volunteer is employed for a variety of studies in phases I and IV of drug development. This type of research can equally be called nontherapeutic in nature. Every experiment involving healthy volunteers should be approved by the Ethics Committee. Using volunteers within the department, company or other organisation, while offering advantages for the investigator should be prohibited as freedom of concept might not be safeguarded. As well, financial incentives may over-persuade individuals, including students, who have low incomes and promote the "professional volunteer". To avoid this problem, French law planned a national register. The potential benefits of such a disposition are still unknown. Having been given appropriate information concerning the drug trial, his obligations and rights, the healthy volunteer gives his written consent. Specific recommendations for nontherapeutic assessments of drug effects are given concerning prisoners, the mentally handicapped, women with a risk of frequency, children. Ethical considerations concerning research on a healthy population must go beyond the law recently promulgated in France.