[Perception of written and oral information by 50 healthy volunteers from a monocentric study]. / Perception de l'information orale et écrite par 50 volontaires sains d'une étude monocentrique.

The purpose of this survey in 50 healthy volunteers from a single-centre study was to assess from a questionnaire filled in by the participants, their comprehension and evaluation of the written and oral information and the legal framework, as well as their uncertainty regarding participation, in terms of age, gender and profession. Overall satisfaction with regard to comprehension and oral information was recorded, but 42% of volunteers considered the informed consent form too long and one-quarter of them did not read it completely. Knowledge of the legal framework (20%) did not influence either their understanding or hesitation to participate. The hesitant individuals (26%) more often judged this framework to be reassuring than the non-hesitant individuals (77% versus 38%; p = 0.015). These findings concerned females, medics or paramedics and younger individuals (< or =35 years). In individuals who do not give their consent, it would be interesting to study the reasons for refusal to participate and the influence of the ethical and legal framework in clinical trials in enhancing the patients' partnership in a context of evidence-based medicine.

Probe of CYP3A by a single-point blood measurement after oral administration of midazolam in healthy elderly volunteers.

BACKGROUND: Midazolam (MDZ) is used as an assessment of human cytochrome P450 3A (CYP3A) activity. A single blood measurement is used as a marker of its activity based on an observed correlation between MDZ clearance and the 1'-hydroxymidazolam (1'-OH-MDZ): MDZ plasma ratio is assessed at 0.5 h followig the intake of a single 7.5 mg oral dose of MDZ in healthy young volunteers. In addition, a 4-h plasma MDZ measurement has been found to be an excellent predictor of AUC and CYP3A activity. OBJECTIVES: The main aim of this study was to define a single-point blood sampling in healthy elderly volunteers. The secondary objective was to investigate the pharmacological effects of a low oral dose of MDZ (5 mg) and its potential psychometric changes. METHODS: Eight healthy elderly Caucasian volunteers participated in a single-dose, open-label, non-comparative study. Each subject received a single 5 mg oral dose of MDZ. Plasma concentrations of MDZ and its major metabolite, 1'-OH-MDZ, were assayed over 12 h. Secondary assessments of critical flicker fusion (CFF), body sway and mini-mental state examination were also carried out during the 12-h post-administration period. RESULTS: A moderate correlation was observed between MDZ clearance and the 1'-OH-MDZ: MDZ plasma concentration ratio at 9 h post-dosing (Rho=0.81; p=0.04), but an even better correlation (Rho=0.99; p<0.009) was found between MDZ AUC and MDZ plasma concentration at 6 h post-dosing, with the latter value corresponding approximately to the average mean residence time (MRT) determined in our trial. This study was well-tolerated despite a significant transitory decrease (relative to baseline) in cortical arousal at 1 h post-dosing, as assessed by CFF, and a non-significant decrease (relative to baseline) in balance and vigilance also measured at 1 h and assessed on body sway, compared to baseline values. CONCLUSION: Despite the small sample size, based on the results of healthy, elderly volunteers, a single MDZ plasma measurement taken at 6 h post-oral administration may represent an accurate marker of CYP3A phenotype. This single-time-point method could be used safely for predicting drug-drug or diet interactions and identifying individuals with genetic polymorphism that affect CYP3A activity.