Pharmacokinetic analysis of diazepam liberation from avizafone in healthy volunteers : Non-compartmental approach and compartmental modeling

Date du colloque&nbsp;: 04/2009</p

Pharmacokinetic analysis of pralidoxime after its intramuscular injection alone or in combination with atropine-avizafone in healthy volunteers

BACKGROUND AND PURPOSE Treatment of organophosphate poisoning with pralidoxime needs to be improved. Here we have studied the pharmacokinetics of pralidoxime after its intramuscular injection alone or in combination with avizafone and atropine using an auto-injector device. EXPERIMENTAL APPROACH The study was conducted in an open, randomized, single-dose, two-way, cross-over design. At each period, each subject received either intramuscular injections of pralidoxime (700 mg), or two injections of the combination: pralidoxime (350 mg), atropine (2 mg), avizafone (20 mg). Pralidoxime concentrations were quantified using a validated LC/MS-MS method. Two approaches were used to analyse these data: (i) a non-compartmental approach; and (ii) a compartmental modelling approach. KEY RESULTS The injection of pralidoxime combination with atropine and avizafone provided a higher pralidoxime maximal concentration than that obtained after the injection of pralidoxime alone (out of bioequivalence range), while pralidoxime AUC values were equivalent. Pralidoxime concentrations reached their maximal value earlier after the injection of the combination. According to Akaike and to goodness of fit criteria, the best model describing the pharmacokinetics of pralidoxime was a two-compartment with a zero-order absorption model. When avizafone and atropine were injected with pralidoxime, the best model describing pralidoxime pharmacokinetics becomes a two-compartment with a first-order absorption model. CONCLUSIONS AND IMPLICATIONS The two approaches, non-compartmental and compartmental, showed that the administration of avizafone and atropine with pralidoxime results in a faster absorption into the general circulation and higher maximal concentrations, compared with the administration of pralidoxime alone

Primary processes: from atoms to diatomic molecules and clusters

International audienceThis article presents a short review of the main progresses achieved at the GANIL facilities during the last thirty years in the field of ion-atom and ion-diatomic molecule collisions. Thanks to the wide range of projectile energies and species available on the different beam lines of the facility, elementary processes such as electron capture, ionization and excitation have been extensively studied. Beside primary collision mechanisms, the relaxation processes of the collision partners after the collision have been another specific source of interest. Progresses on other fundamental processes such as Young type interferences induced by ion-molecule collisions or shake off ionization resulting from nuclear beta decay are also presented. 1. Introduction For the electronic structures of atoms and molecules, precise theoretical knowledge and high-resolution experimental data are available. But the complete understanding of dynamic processes in atomic collisions remains a challenge, due to large theoretical problems in describing time-dependent many-particle reactions, and to experimental difficulties in performing complete experiments in which all relevant quantities are accessible. Elementary collisions involving ions, atoms and molecules play an important role in many gaseous and plasma environments, where they provide both the heating and cooling mechanisms. The study of such collisions is thus not only of fundamental importance, it is also essential for the understanding of large-scale systems such as astrophysical plasmas, planetary atmospheres, gas discharge lasers, semiconductor processing plasmas, and fusion plasmas. Collisions between ions and atoms (or simple molecules) give also access to the elementary processes responsible for energy transfer in ion-matter and ion-biological molecule collisions. Complete knowledge of these elementary processes is thus of primordial importance for ion induced modification of materials as well as for radiolysis, radiotherapy and biological damages due to radiation exposure