Plasma Protein and Lipoprotein Distribution of Clozapine

Abstract

In plasma samples with elevated triglycerides, clozapine shifts from the lipoprotein-deficient fraction to the very-low-density lipoprotein fraction. This redistribution of clozapine may affect the pharmacological activity of clozapine.

Association between Serum Lipids and Antipsychotic Response in Schizophrenia

“…One proposed mechanism suggests that serum lipids may alter the pharmacokinetics of antipsychotics. To this end, we have shown that clozapine redistributes itself from the lipoprotein-deficient fraction to the low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) fractions as serum TG concentrations increased [40]. This is in line with a recent study showing that lipophilic compounds with extensive hepatic metabolism (e.g., clozapine) have a strong tendency to associate with lipoproteins, in particular, LDL and VLDL [41].…”

The in Vitro Plasma Distribution of a Novel Cholesteryl Ester Transfer Protein Inhibitor, Torcetrapib, Is Influenced by Differences in Plasma Lipid Concentrations

“…Preliminary studies from our group and others have suggested that the association of therapeutic compounds with lipoproteins can alter the pharmacokinetics, efficacy, and toxicological profile of the compound (20,21). Lipoproteins have been found to be carriers of many hydrophobic drugs, and the lipid profile of the patient can alter the lipoprotein distribution of the therapeutic compound with significant clinical implications (20).…”

Smoking, components of metabolic syndrome and clinical severity of schizophrenia

“…Key words: body mass index; glucose; lipids; schizophrenia; smoking kova [6][7][8][9][10] . Primjerice, opaženo je da premještanje antipsihotika vezanih za serumske albumine u lipidne frakcije LDL kolesterola (engl.…”

“…low density lipoprotein cholesterol) i VLDL kolesterola (engl. very low density lipoprotein cholesterol) koje ujedno predstavljaju i važno fiziološko skladište antipsihotičnih lijekova modulira njihovu farmakokinetiku; dovodi do povećanja njihove aktivne koncentracije te olakšava transport antipsihotika kroz krvno-moždanu barijeru 6,8 . Nadalje, uočeno je da povećanje tjelesne mase prati porast koncentracije leptina u mozgu; leptin se smatra važnim modulatorom dopaminergičke neurotransmisije 10 , pri čemu se poseban značaj pripisuje inhibitornom učinku leptina na pojačanu dopaminergičku aktivnost u prefrontalnom korteksu, budući da se ona povezuje s pozitivnim simptomima shizofrenije 6,9,10 .…”

“…very low density lipoprotein cholesterol) koje ujedno predstavljaju i važno fiziološko skladište antipsihotičnih lijekova modulira njihovu farmakokinetiku; dovodi do povećanja njihove aktivne koncentracije te olakšava transport antipsihotika kroz krvno-moždanu barijeru 6,8 . Nadalje, uočeno je da povećanje tjelesne mase prati porast koncentracije leptina u mozgu; leptin se smatra važnim modulatorom dopaminergičke neurotransmisije 10 , pri čemu se poseban značaj pripisuje inhibitornom učinku leptina na pojačanu dopaminergičku aktivnost u prefrontalnom korteksu, budući da se ona povezuje s pozitivnim simptomima shizofrenije 6,9,10 . Konačno, zanimljiva je i korelacija metabolizma glukoze i dopaminergičke neurotransmisije; opaženo je da upotreba anatogonista dopamina pridonosi većoj koncentraciji glukoze i inzulina u plazmi štakora 11 , a u humanoj je populaciji uočena povezanost između parametara promijenjenog metabolizma glukoze s težinom kliničke slike shizofrenije, iako rezultati studija nisu ujednačeni [12][13][14][15] .…”