EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 2007, Vol. 32, No.2, pp. 87-99 Adapting therapy with repeated short-infusions to inter individual variability between patients J.D. ROSCA I and J.M. VERGNAUD 2 IDepartment of Polymer Chemistry, Polytechnic University, Bucharest, Romania; 2University of Saint-Etienne, Saint-Etienne, France Received/orpublication: October 232006 Key words: Intravenous administration, short infusion, inter individual variability, adapted therapy, pharmacoki- netics, modelling, master curves SUMMARY Because of the wide inter individual variability between patients and their marked differences in drug response, one of the major issues that arises is adapting the therapy in question to the particular patient. In hospital, it is possible to vary the conditions of intra- venous (i.v.) drug delivery by means of short infusions repeated at certain intervals. In this study, review of this process has been presented, and a therapeutic method described. It essentially consists of two stages. The first concerns the time of the first infusion, and the course of drug elimination: from two analyses of the drug concentrations in the blood made at two different times, the phar- macokinetic parameters of the patient are determined. Stage 2 consists of repeated short infusions and the therapy is adapted to the particular patient by varying the conditions involved. Thus, either the amount of the dose based on the rate of infusion or the time interval between the repeated infusions are varied. In order to reach a general solution, master curves are built by using dimen- sionless numbers as co-ordinates, such as time expressed in terms of the half-life tos of the drug, and the drug concentration at the peaks defined as a fraction of the first unchanged peak concentration. INTRODUCTION Modem drug development has become an increas- ingly time-consuming and expensive process. A long laboratory R&D phase is followed by extensive testing in clinical trials; then the FDA (Food & Drug Administration) painstakingly reviews the results before the drug candidate can obtain fmal approval. Given these requirements, the development of a drug can takes more the 15 years of work and hundreds of millions of dollars in costs, without speaking about the thousands of dead-end research avenues. And so it is a great pity when an accident occurs, not only for 'Please send reprint requests to: Prof. J.M. Vergnaud, Che- min prive de Grange Bruyas, Route de Chavanne, 42400, Saint-Chamond, France vergnaud.jean-maurice@wanadoo.fr the patients who are those directly concerned but also for the therapists as well as for the companies in- volved in manufacturing the drug. Following the alarming events caused by COX-2 Vioxx in 2005, the FDA is attempting to improve the system by taking steps to better monitor the safety of marketed drugs. But a drug is an active agent, meaning that it acts on the patient's body in general, not only on an isolated organ but also throughout the organism, leading to what is called side-effects. The importance of these side-effects depends on the patient's capacity to respond positively to the drug in question; and thus the inter individual variability between patients should be taken into serious consid- eration. Moreover, it would be advisable to adapt the treatment to the patient by taking into account his particular pharmacokinetic parameters. Adapting therapy with the administration of oral dosage forms,