In vitro P-glycoprotein efflux inhibition by atypical antipsychotics is in vivo nicely reflected by pharmacodynamic but less by pharmacokinetic changes

► We investigated atypical antipsychotics and their interaction with P-gp at the BBB. ► Inhibitory potency, pharmacokinetics and pharmacodynamics were investigated. ► Amisulpride, N-desmethylclozapine, olanzapine and quetiapine are substrates of P-gp. ► Ranking of drugs for inhibitory potency is reflected in their pharmacodynamics. ► Pharmacodynamic effects were best correlated to brain levels not accessible in humans.