![]() This phenotype was confirmed when performing in vitro assay with the active ( R)-PZQ, while at a similar concentration of ( S)-PZQ, the worms became instead transiently hyperactive. ![]() mansoni adult worms to PZQ leads to two striking phenomena in vitro: an almost instantaneous spastic paralysis of the parasite musculature and a rapid structural damage of the tegument. The latter was then converted into single oral dose at (40 or 60 mg/kg) with similar efficacy in MDAs, leaving some flexibility in dosing regimen for NCEs. (11,12) While it is unknown whether these findings in the mouse can be extrapolated to humans, clinically, PZQ’s dosing regimen was first segmented during 1 day (20 mg/kg t.i.d.). a scaling issue rather than a drug metabolism issue. (10) A single high oral dose of 400 mg/kg in the mouse model could be explained by the absolute drug concentrations required before first pass metabolism, i.e. However, estimated portal vein drug concentrations predicted better the efficacy of PZQ, indicating that exposure prior to the first pass metabolism in the liver is critical. mansoni mouse model is not predictive of efficacy. mansoni adult worms live in the mesenteric veins, and systemic plasma exposure of PZQ in the S. migrate through various host organs for their maturation to finally reside in two main final target organs, the gut and the bladder.
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