We appreciate both the interest in our work and the submitted comments. CitationThiermann et al. correctly point out that DFP has a comparably low rate of inhibition. Its ki value is 3 orders of magnitude lower than that of VX, 2 orders of magnitude lower than that of tabun and about one tenth of that of paraoxon-ethyl (CitationWorek et al. 2004). In addition, the affinity of established oximes to AChE inhibited by DFP is considerably higher than after exposure to VX. We also agree without reservations with the statement that “efficacy of oximes is strongly dependent on the OP compound” and that “the therapeutic effect of oximes in DFP poisoning does not necessarily imply a comparable therapeutic effect in poisoning by other OP compounds”.
These are the reasons why, over time, our group systematically examined the efficacy of oximes against a number of OP compounds, both in vitro and in rodents. The newly developed oximes K-27 and K-48 protect AChE in vitro from inhibition by VX, tabun and paraoxon-ethyl and have superior life preserving properties after exposure to these OP compounds in vivo (CitationKuča et al. 2005; CitationKassa et al. 2006; CitationPetroianu and Kalasz 2007).
A human AChE source, such as red blood cells, is indeed a suitable model system to assess the effect of OP compounds and oximes upon the synaptic enzyme, and this surrogate system has been used to evaluate the protective effect of K-27 and K-48 upon red blood cell AChE inhibited by DFP (CitationLorke et al. 2008). The predictive value of in vitro derived results for in vivo efficacy is, however, not satisfactory in our model (CitationPetroianu and Lorke, 2008). We therefore prefer survival as an objective indicator for therapeutic efficacy, with all the caveats of extrapolation the correspondence reminds us of.
References
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