title: Lomitapide affects HDL composition and function.
abstract: Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-density lipoprotein-cholesterol (HDL-C) levels. The latter may reduce the clinical efficacy of lomitapide. We investigated the effect of lomitapide on HDL-C levels and on cholesterol efflux capacity (CEC) of HDL in patients with homozygous familial hypercholesterolemia (HoFH).
  
  
  
  Four HoFH patients were treated with increasing dosages of lomitapide. Lomitapide decreased LDL-C (range -34 to -89%). Total HDL-C levels decreased (range -16 to -34%) with a shift to buoyant HDL. ABCA1-mediated CEC decreased in all patients (range -39 to -99%). The changes of total, ABCG1- and SR-BI-mediated CEC were less consistent.
  
  
  
  Lomitapide decreased LDL-C and HDL-C levels. Our report raises the hypothesis that the anti-atherogenic potential of HDL seems to be unaffected as total CEC did not seem to change consistently. Combined with the reduction of atherogenic lipoproteins, the net effect of lomitapide appears to be beneficial in HoFH patients.
authors.affiliation: Department of Internal Medicine, Division Pharmacology, Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Yahya
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Favari
authors.affiliation: Centro Grosi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Calabresi
authors.affiliation: Department of Internal Medicine, Division Pharmacology, Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: A J M
authors.initials: AJM
authors.lastname: Verhoeven
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Zimetti
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Adorni
authors.affiliation: Centro Grosi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gomaraschi
authors.affiliation: Department of Internal Medicine and Medical Specialties - DIBIMIS, School of Medicine, University of Palermo, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Averna
authors.affiliation: Department of Internal Medicine and Medical Specialties - DIBIMIS, School of Medicine, University of Palermo, Palermo, Italy.
authors.forename: A B
authors.initials: AB
authors.lastname: Cefalù
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bernini
authors.affiliation: Department of Internal Medicine, Division Pharmacology, Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: E J G
authors.initials: EJG
authors.lastname: Sijbrands
authors.affiliation: Department of Internal Medicine, Division Pharmacology, Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Mulder
authors.affiliation: Department of Internal Medicine, Division Pharmacology, Vascular and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: j.roetersvanlennep@erasmusmc.nl.
authors.forename: J E
authors.initials: JE
authors.lastname: Roeters van Lennep
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000328:Adult; D050197:Atherosclerosis; D001562:Benzimidazoles / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood* / Q000187:drug effects*; D008297:Male; D010641:Phenotype; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; C473731:BMS201038; D001562:Benzimidazoles; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D002784:Cholesterol
keywords: Cholesterol efflux capacity; Cholesterol lowering drugs; HDL; Homozygous familial hypercholesterolemia; Lomitapide