[Literature review on pharmacovigilance of medicines derived from traditional pharmacopoeias. Part I: Risks identification]. / Revue de la littérature sur la pharmacovigilance des médicaments issus des pharmacopées traditionnelles. Partie I : identification des risques.

Globally, the use of drugs from traditional pharmacopoeias is a major subject. The confidence of the populations in these drugs is linked to their presumption of safety and also to the fact that geographically and financially they are more accessible than synthetic drugs. In view of the high exposure of the world population to traditional medicines, they are subject to pharmacovigilance guaranteeing their safety in use. Thus, this review aims to take stock of the risks identified by the national pharmacovigilance systems. It is based on research referenced in PubMed, Embase, ScienceDirect and GoogleScholar. These studies indicate that the use of traditional drugs can involve risks including adverse effects, interactions with synthetic drugs, adulteration and contamination. The spontaneous notification system was the basis for their identification. Strengthening this system and making populations aware of these risks constitute the key levers for traditional medicines pharmacovigilance progress.

[Literature review on pharmacovigilance of medicines derived from traditional pharmacopoeias. Part II: Risks assessment and prevention]. / Revue de la littérature sur la pharmacovigilance des médicaments issus des pharmacopées traditionnelles. Partie II : évaluation et prévention des risques.

After the initial stage of the pharmacovigilance process for medicines from traditional pharmacopoeias - which concerns the identification of the risks associated with their use - the risk assessment should now be approached. The latter makes it possible to detect potential signals early and to take preventive measures. We sought to understand, from a review of the literature, the steps and methods of risk assessment relating to traditional medicines, as well as the prevention strategies applied to them. All of the work carried out on the subject has shown that the steps and methods for assessing and preventing drug risks are the same for both conventional and traditional medicines. Risk assessment includes analysis of the quality of individual notifications, assessment of causality, detection and evaluation of signals. The World Health Organization method is the most widely used for causality assessment internationally, while disproportionality measures are the most applied for signal detection. Regarding prevention, risk communication is the main strategy for the risks associated with traditional medicines. This review suggests the involvement of traditional medicine practitioners both in the notification system and in the communication strategy on the risks associated with their products.

[Phytovigilance: A medical requirement and a legal obligation]. / La phytovigilance: impératif médical et obligation légale.

Phytovigilance consists in supervision of side effects and drug interactions consequential to use of herbal medicinal products, herbal food supplements, herbal cosmetics and/or medicinal plants. It includes thus pharmacovigilance applied to phytotherapy, nutrivigilance and cosmetovigilance but also addictovigilance in case of plants, which lead to drug addiction, and toxicovigilance in case of toxic plants. Becoming necessary owing to (acute or chronic) toxicity risks or to drug interactions risks (of pharmacocinetical or pharmacodynamical kind)--as far as it concerns interactions between several associated plants or between a plant and a chemical or biotechnological allopathic medicine--phytovigilance represents moreover a legal obligation. Pharmacovigilance--in case of herbal medicinal products--is indeed becoming mandatory according to title IX of the European directive 2001/83/EC, whereas nutrivigilance is imposed by the European Food Safety Agency (EFSA).

[Orphan drugs: some legal, ethical and economics aspects]. / Médicaments orphelins: quelques aspects juridiques, éthiques et économiques.

Besides well-known diseases, about 5,000 identified are classed as "orphan" because of the lack of any response in terms of diagnosis, prevention and treatment. The development of drugs for these diseases, intended for a limited number of patients, often requires considerable research, and subsequently, cost. The aim of the present article is to discuss the ethical, political and economic problems relevant to the development and disposal of drugs specifically designed for these diseases, now commonly called "orphan" drugs. These questions have been raised at discussions and dialogues at the European Parliament where European regulations on orphan drugs were adopted on December 15, 1999. These regulations (141/2000/EEC) came into effect in the European Union on January 22, 2000, and are widely inspired from the American model. The regulations stipulate that the criterion for designation of the drug is based on a disease prevalence of 5/10000). Advantages commonly recognized for the orphan drug status concern: community registration (centralized marketing approval), eligibility for grants and national or community fiscal support, lower or canceled registration fees, technical contribution via the European drug agency (EMEA), and exclusive rights for a 10-year period. On May 12, 2000, the European Commission completed the status by adopting rules establishing the criteria used for designating a drug as an orphan drug. This document implements the dispositions available to pharmaceutical firms inciting them to invest in the development of orphan drugs.

Enantiomeric determination of tramadol and its main metabolite O-desmethyltramadol in human plasma by liquid chromatography-tandem mass spectrometry.

Pharmacokinetic studies require sensitive analytical methods to allow the determination of low concentrations of drugs and metabolites. When drugs present an asymmetric center, the enantiomeric determination of the compounds of interest should be performed. The method developed is based on on-line LC-MS-MS using atmospheric pressure chemical ionization as an interface determination of enantiomers of tramadol (T) and its active metabolite O-desmethyltramadol (ODT) in human plasma. This determination is preceded by an off-line solid-phase extraction (SPE) on disposable extraction cartridges (DECs), performed automatically by means of a sample processor equipped with a robotic arm (ASPEC system). The DEC filled with ethyl silica (50 mg) was first conditioned with methanol and water. The washing step was performed with water and the analytes were finally eluted by dispensing methanol. The collected eluate was then evaporated to dryness before being dissolved in the LC mobile phase and injected into the LC system. The enantiomeric separation of tramadol and ODT was achieved on a Chiralpak AD column containing amylose tris-(3,5-dimethylphenylcarbamate) as chiral selector. The mobile phase was isohexane-ethanol-diethylamine (97:3:0.1, v/v). The LC system was then coupled to a tandem mass spectrometry system with an APCI interface in the positive ion mode. The chromatographed analytes were detected in the selected reaction monitoring mode. The MS-MS ion transitions monitored were 264-->58 for tramadol, 250-->58 for ODT, and 278-->58 for ethyltramadol, used as internal standard. The method was validated. The recoveries were around 90% for both T and ODT. The method was found to be linear for each enantiomer of both compounds (r2>0.999). The mean RSD values for repeatability and intermediate precision were 3.5 and 6.4% for T enantiomers and 5.0 and 5.6% for ODT enantiomers, respectively. Moreover, the method was found to be selective towards other metabolites, N-desmethyltramadol and N,O-desmethyltramadol (NODT). The method developed was successfully used to investigate plasma concentration of enantiomers of T and ODT in a pharmacokinetic study.

Alanine-ESR in vivo dosimetry: a feasibility study and possible applications.

A new alanine-ESR dosimeter has been developed at AERIAL in order to study its potential use in radiotherapy. Alanine-ESR results are compared with ion chamber for depth-dose measurements. A good concordance has been found between provisional dosimetry and absorbed dose during high dose rate and intra operative treatments. The results of the experiments indicate that alanine-ESR dosimetry is suited to check dose optimisation routines and seems to be a promising in vivo dosimetry technique.