Efficacy of telavancin against penicillin-resistant pneumococci and Staphylococcus aureus in a rabbit meningitis model and determination of kinetic parameters

The penetration of telavancin was 2% into inflamed meninges and ca. 1 per thousand into noninflamed meninges after two intravenous injections (30 mg/kg of body weight). In experimental meningitis, telavancin was significantly superior to vancomycin combined with ceftriaxone against a penicillin-resistant pneumococcal strain. Against a methicillin-sensitive staphylococcal strain, telavancin was slightly but not significantly superior to vancomycin.

Kinetic simulation of neutral∕ionized gas and electrically charged dust in the coma of comet 67P∕Churyumov-Gerasimenko

The cometary coma is a unique phenomenon in the solar system being a planetary atmosphere influenced by little or no gravity. As a comet approaches the sun, the water vapor with some fraction of other gases sublimate, generating a cloud of gas, ice and other refractory materials (rocky and organic dust) ejected from the surface of the nucleus. Sublimating gas molecules undergo frequent collisions and photochemical processes in the near‐nucleus region. Owing to its negligible gravity, comets produce a large and highly variable extensive dusty coma with a size much larger than the characteristic size of the cometary nucleus. The Rosetta spacecraft is en route to comet 67P/Churyumov‐Gerasimenko for a rendezvous, landing, and extensive orbital phase beginning in 2014. Both, interpretation of measurements and safety consideration of the spacecraft require modeling of the comet’s dusty gas environment. In this work we present results of a numerical study of multispecies gaseous and electrically charged dust environment of comet Chyuryumov‐Gerasimenko. Both, gas and dust phases of the coma are simulated kinetically. Photolytic reactions are taken into account. Parameters of the ambient plasma as well as the distribution of electric/magnetic fields are obtained from an MHD simulation [1] of the coma connected to the solar wind. Trajectories of ions and electrically charged dust grains are simulated by accounting for the Lorentz force and the nucleus gravity.

Optimized on-line enantioselective capillary electrophoretic method for kinetic and inhibition studies of drug metabolism mediated by cytochrome P450 enzymes.

Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly differ between application of the racemate and single enantiomers. During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on-line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion-based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter-scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated γ-cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost-effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450-mediated metabolic steps within early stages of the development of a new drug.