Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

Maintenance process development for remote administration of network servers

Maintenance is a part of system development and it is possible to develop operation models for accomplishing maintenance tasks. These models can be applied to individual maintenance tasks, maintenance projects and version management. Beneficial operation models makes maintenance more effective and they assist in managing various changes. The purpose of this thesis was to develop a maintenance process which can be used to remote administer network servers. This consisted of defining those operation models and technical specifications which enable to set up, manage changes, maintain and monitor resources of information systems that are located in several different sites. At first in this thesis the needs of the process were determined and requirements were defined based on those needs. The meaning of processes in maintenance of information systems, maintenance workflows and challenges were studied. Then current practical problems and disadvantages of maintenance work were analyzed in order to focus the development to proper issues. Because available operation models did not cover all the recent needs, new maintenance process which fulfilled the requirements was developed.

Is Inefficiency under control in the Justice Administration?

Efficiency in the administration of justice is found to increase over time, while the variation in the efficiency of the courts tended to remain low and fall over time. This would appear to be good news, at least for the case studied here: the civil courts of first instance in Spain between 2005 and 2009. Apart from the simple passing of time, the percentage of temporary judges in the system also determines some of the differences in efficiency between courts over time. Thus, we find that the greater the percentage of temporary judges, the lower is the efficiency of the courts. Overall, the average relative efficiency level for the period 2005 to 2009 was 97.46%, suggesting the matter is under control.

Annales de l'Institut national agronomique : administration, enseignement et recherche

1919 (SER2,T14).