Distribution of Psychotropic Drugs Into Lipoproteins

Abstract

The aim of this pilot study was to investigate whether psychotropic drugs frequently analyzed in a routine therapeutic drug monitoring (TDM) laboratory bind to low density lipoproteins/very low-density lipoproteins (LDL/VLDL) in human serum. METHODS:Drug concentrations in 20 serum sample pools containing one psychotropic drug each, and in the LDL/VLDL fractions extracted from the same samples, were measured by triple quadrupole liquid chromatography tandem mass spectrometry (LC-MS/MS). The membrane permeability of the drugs was measured using a Parallel Artificial Membrane Permeability Assay (PAMPA). RESULTS:Out of the 20 antidepressants, antipsychotics and antiepileptics examined, seven drugs were detected in both the pooled serum samples and in the LDL/VLDL fraction.Binding of drugs to LDL/VLDL significantly correlated with high octanol:water partition coefficient (logP), high degree of protein binding (PB) and a low polar surface area (PSA).The drugs found in LDL/VLDL, with the exception of aripiprazole, were also characterized by high or intermediate membrane permeability. CONCLUSIONS:The present results indicate that psychotropic drugs with certain characteristics bind to LDL/VLDL in blood. This further implies that lipoproteins could play an important role in drug transport.