Kyawt Mon Win, Kyaw Lwin Show, Jetsumon Sattabongkot, Pyae Linn Aung
Ownership and use of insecticide-treated nets in Myanmar: insights from a nationally representative demographic and health survey
Malaria journal
crossspecies differences drug transport metabolism linked poor translation preclinical pharmacokinetic toxicology data humans often resulting failure new chemical entities nces clinical drug development specifically inaccurate prediction renal clearance renal accumulation nces due differential abundance enzymes transporters kidneys lead differences pharmacokinetics toxicity experimental animals humans carried liquid chromatographytandem mass spectrometry lcmsmsbased protein quantification 78 membrane drugmetabolizing enzymes transporters dmets kidney membrane fractions humans rats mice characterization crossspecies sexdependent differences general majority dmet proteins higher rodents humans significant crossspecies differences observed 30 33 membrane dmet proteins quantified three species although significant sexdependent differences observed humans abundance 28 46 membrane proteins showed significant sex dependence rats mice respectively crossspecies sexdependent quantitative abundance data valuable gaining mechanistic understanding drug renal disposition accumulation data also integrated systems pharmacology tools physiologically based pharmacokinetic models enhance interpretation preclinical pharmacokinetic toxicological data