Differential Calculus By Das And Mukherjee.pdf ^NEW^ 💻
Differential Calculus By Das And Mukherjee.pdf ^NEW^ 💻
Differential Calculus By Das And Mukherjee.pdf
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Triazolopyrimidines have been shown to be highly active in vitro against a series of Plasmodium falciparum isolates with known resistance mechanisms. The aim of the current study was to identify in vitro, ex vivo and in vivo factors that influence the pharmacodynamic, pharmacokinetic and toxicological profile of these compounds. In the ex vivo assays, toxicity was low and IC50 values were in agreement with the high EC50 values observed in the in vitro parasite growth inhibition assay. The most significant difference between wild-type and resistant strains was a shorter half-life in the resistant strains. This was confirmed in the ex vivo and in vivo assays. No difference in absorption rate was observed, however, differences in absorption and/or distribution were observed. The presence of alternative transport systems in the resistant strains was excluded. No genotypic polymorphism was detected in the candidate genes investigated (Pfmdr1, Pfmrp, Adr1). However, single nucleotide polymorphisms in Pfmdr1 and Pfmrp were identified in the resistant strains. In total, only four of the candidate genes investigated could explain the reduced susceptibility of the resistant isolates. In conclusion, despite the promising potential of this class of anti-malarial compounds, these results suggest that resistance may be difficult to overcome.Q:
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