The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

In vitro correlates of benzodiazepine cerebrospinal fluid uptake, pharmacodynamic action and peripheral distribution.

Factors influencing the rate and extent of benzodiazepine uptake into cerebrospinal fluid (CSF), peripheral tissue distribution and electroencephalographic (EEG) effects were evaluated in a model utilizing anesthetized male cats. A single (0.25-10 mg/kg) dose of the following eight benzodiazepines was administered i.v.: diazepam, desmethyldiazepam, midazolam, lorazepam, alprazolam, triazolam, flunitrazepam and clobazam. Multiple samples were simultaneously drawn from arterial blood and cisternal CSF over the next 4 hr and the EEG was continuously monitored. Concentrations of benzodiazepines in plasma and CSF samples were measured by electron-capture gas-liquid chromatography and plasma protein binding determined by equilibrium dialysis. Physicochemical properties of lipophilicity of each benzodiazepine were determined by measurement of the octanol/buffer partition ratio at physiologic pH and by the high-pressure liquid chromatographic (HPLC) retention on a reverse-phase C18 column at neutral pH. Disappearance of all benzodiazepines from plasma was consistent with a linear sum of two or three exponential terms. After correction for individual differences in protein binding, volume of distribution (Vd) of unbound drug was highly correlated with HPLC retention (r = 0.91), but not significantly related to octanol/buffer partition coefficient. Diazepam and midazolam, having the longest HPLC retention also had the largest unbound Vd. All benzodiazepines rapidly entered CSF, with peak concentrations usually attained within 15 min of dosage. More lipophilic drugs tended to enter CSF most rapidly, but associations of entry rate and in vitro lipophilicity were not significant. After distribution equilibrium was attained, disappearance of benzodiazepines from both plasma and CSF occurred in parallel. Equilibrium CSF/total plasma concentration ratios of all drugs were much less than unity.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

References

  1. In vitro correlates of benzodiazepine cerebrospinal fluid uptake, pharmacodynamic action and peripheral distribution. Arendt, R.M., Greenblatt, D.J., deJong, R.H., Bonin, J.D., Abernethy, D.R., Ehrenberg, B.L., Giles, H.G., Sellers, E.M., Shader, R.I. J. Pharmacol. Exp. Ther. (1983) [Pubmed]
 
WikiGenes - Universities