SUMMARYAntidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D 2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D 2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT 3 ) and 5-HT 4 receptors for metoclopramide; 5-HT 4 receptors for levosulpiride) and ability to permeate the bloodbrain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT 4 ) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D 2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D 2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D 2 receptor (i.e. compounds that bind loosely to D 2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D 2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/ benefit ratio.

. Under the EMEA centralised procedure, several active substances have been licensed for children. Consequently serious and life-threatening diseases as AIDS and diabetes are now treatable, in a legal framework overcoming the orphan status of the past years. Despite the reported encouraging results, the number of drugs devoted to children remain low and important ATC classes, as L-(oncology) or N-(neurology), are still 'orphans' of innovative medicines. At the same time few medicinal products are specifically studied in children. Consequently, more efforts have to be made to increase the number of drugs assessed and licensed for the paediatric population, and manufacturers should be required to supply data on the effects of new drugs in children when the products are expected to offer a benefit over existing therapies.

INTRODUZIONELa costruzione di un sistema farmaceutico europeo dotato di regole comuni a tutti i Paesi Membri è iniziata nel 1965 ed ha subìto un'importante svolta nel 1992, con l'adozione di un sistema comune di registrazione e l'istituzione della European Medicines Evaluation Agency (EMEA).Il nuovo sistema, già operativo dal gennaio 1995, si prefigge la realizzazione di un mercato unico nel settore farmaceutico, nonché il raggiungimento di un più alto livello di salute e sicurezza per i cittadini, garantendo la disponibilità di prodotti farmaceutici di qualità elevata, innovativi rispetto agli esistenti e basati su più solide evidenze scientifiche. ABSTRACTThe european pharmaceutical market doesn't seem to be a common integrated european market as far as prices and reimbursements within different countries are concerned. Moreover, to better define such differences, little information is available because of the lack of homogeneous and updated european databases. The aim of this study is to assess mutual availability, prices and reimbursements of innovative drugs authorised by EMEA under European Centralised Procedure between 1995-2000 and marketed in five european countries (Italy, Spain, United Kingdom, France and Denmark). Our results demonstrate that the adoption of different drug-price definition models, within different Member States, is the main cause of the heterogeneity. Currently, in countries adopting a controlled drug-price system, prices are lower than prices set in countries that adopt an uncontrolled drug-price system. In this regard, Italy ranks in a middle position as products marketed in Italy generally have prices lower than in the United Kingdom and Denmark, and higher than in France and Spain. Product availability and level of drug breakthrough in the national markets seem to greatly affect the variations we noted among prices and reimbursements in different countries. Differences we observed emphasize the need of finding a common methodology at european level, in order to define the proven "therapeutic benefit" and the "therapeutic advantage" of innovative drugs, allowing a "right price" and reimbursement to the entitled. Farmeconomia e percorsi terapeutici 2002; 3 (1): 15-27Sotto il profilo regolatorio, l'introduzione di un'unica procedura di registrazione (Procedura Centralizzata), simultaneamente valida in tutti i quindici Stati Membri, se da un lato ha comportato una notevole semplificazione dell'iter registrativo dei farmaci, dall'altro lato ha reso imperativo: -individuare validi criteri oggettivi, armonizzati e fondati su ampio consenso, atti a definire l'innovazione come principio su cui fondare l'accesso alla Registrazione Centralizzata, secondo la parte B dell'Annex del Reg. CE 2309/93 (1); -definire il valore terapeutico dei nuovi farmaci, come discriminante in base alla quale individuare e reperire le risorse necessarie ANALISI ECONOMICA

Because the acceptance criteria required by the drug regulatory agency (European Medicines Agency, EMA) for bioequivalence prescribe limits of 80%-120% for untransformed data and 80%-125% for "ln" transformed data, we can confirm that the 2 formulations are bioequivalent, in terms of the rate and extent of absorption.