RESUMEN
ABSTRACT: The authors describe a patient with substance use disorder admitted to the hospital with septic shock and multiorgan failure, in whom the serum concentration of methadone kept increasing despite discontinuation of the drug. Therapeutic drug monitoring was performed to monitor the methadone serum concentration during treatment of the underlying diseases.
Asunto(s)
Sepsis , Choque Séptico , Humanos , Metadona/uso terapéutico , Insuficiencia Multiorgánica/etiología , Pronóstico , Sepsis/tratamiento farmacológico , Choque Séptico/tratamiento farmacológicoRESUMEN
AIM: The aim of this pilot study was to investigate whether psychotropic drugs frequently analyzed in a routine therapeutic drug monitoring 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. The membrane permeability of the drugs was measured using a Parallel Artificial Membrane Permeability Assay. RESULTS: Of the 20 antidepressants, antipsychotics, and antiepileptics examined, 7 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, and a low polar surface area. 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.