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41.
The effective use of activated charcoal as an oral adsorbent for primary treatment of acute poisoning was investigated in vitro by evaluating the characteristics of mexiletine, an anti-arrhythmic drug, adsorbed onto activated charcoal in the presence of sodium chloride solutions at various concentrations. The equilibrium amount of mexiletine adsorbed onto activated charcoal was increased by the addition of sodium chloride. In particular, there was a marked increase in the amount adsorbed from a solution of lower mexiletine concentration. The removal rate is another important factor in the evaluation of activated charcoal, and a rapid decrease of mexiletine concentration by the addition of sodium chloride was recognized. The acceleration of mexiletine adsorption onto activated charcoal by the addition of sodium chloride was due to the occurrence of salting-out. It could be concluded that the administration of activated charcoal suspended in saline solution was more effective in the primary treatment of acute poisoning by mexiletine overdose. 相似文献
42.
In the post-genome-sequencing era, emerging genomic technologies are shifting the paradigm for drug discovery and development.
Nevertheless, drug discovery and development still remain high-risk and high-stakes ventures with long and costly timelines.
Indeed, the attrition of drug candidates in preclinical and development stages is a major problem in drug design. For at least
30% of the candidates, this attrition is due to poor pharmacokinetics and toxicity. Thus, pharmaceutical companies have begun
to seriously re-evaluate their current strategies of drug discovery and development. In that light, we propose that a transport
mechanism-based design might help to create new, pharmacokinetically advantageous drugs, and as such should be considered
an important component of drug design strategy. Performing enzyme- and/or cell-based drug transporter, interaction tests may
greatly facilitate drug development and allow the prediction of drug–drug interactions. We recently developed methods for
high-speed functional screening and quantitative structure–activity relationship analysis to study the substrate specificity
of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide a practical
tool to screen synthetic and natural compounds, and these data can be applied to the molecular design of new drugs. In this
review article, we present an overview on the genetic polymorphisms of human ABC transporter ABCG2 and new camptothecin analogues
that can circumvent AGCG2-associated multidrug resistance of cancer. 相似文献