Prediction of paclitaxel pharmacokinetic based on in vitro studies: Interaction with membrane models and human serum albumin.

摘要: Abstract Interactions of paclitaxel (PTX) with models mimicking biological interfaces (lipid membranes and serum albumin, HSA) were investigated to test the hypothesis that set in vitro assays proposed can be used predict some aspects drug pharmacokinetics (PK). PTX membrane partitioning was studied by derivative spectrophotometry; effect on biophysics evaluated dynamic light scattering, fluorescence anisotropy, atomic force microscopy synchrotron small/wide-angle X-ray scattering; distribution/molecular orientation assessed steady-state/time-resolved computer simulations. binding HSA quenching, spectrophotometry dynamic/electrophoretic scattering. high is consistent its efficacy crossing cellular off-target distribution. closely located phospholipids headgroups, also interacting hydrophobic chains, causes a major distortion alignment phospholipids, which, together fluidizing effect, justifies toxic effects. binds strongly HSA, which reduced distribution target tissues toxicity bioaccumulation. In conclusion, described biomimetic techniques has potential for early prediction PK issues, alerting required optimizations, potentially minimizing number animal tests development process.