title: Expression and activity of P-glycoprotein (MDR1/ABCB1) in peripheral blood mononuclear cells from patients with anorexia nervosa compared with healthy controls.
abstract: OBJECTIVE
  Pharmacotherapeutic strategies for treatment of anorexia nervosa (AN) are characterized by limited success. Some drugs used (antipsychotics, selective serotonin reuptake inhibitors) are transported by P-glycoprotein (P-gp), a transporter with major impact on pharmacokinetics of substrate drugs. Biochemical alterations seen in AN patients could lead to increased expression and/or activity of P-gp and therefore to diminished access of drugs to the brain. The aim of our study was to investigate expression and activity levels of P-gp in peripheral blood mononuclear cells (PBMCs) in AN patients.
  
  
  METHODS
  PBMCs of 16 AN patients and 16 controls were isolated. Activity of P-gp was determined by flow cytometry and expression was quantified by reverse-transcriptase-real-time-polymerase-chain-reaction.
  
  
  RESULTS
  Neither a significant difference in P-gp expression (AN: 0.00154 +/- 0.00088 [MDR1/beta2 mg], control: 0.00244 +/- 0.0013 [MDR1/beta2 mg], p = .138) nor a difference in P-gp activity (rhodamine 123 ratio AN: 1.79 +/- 0.73, control: 2.03 +/- 0.42, p = .20) between AN patients and healthy controls could be detected. In contrast to previous studies, expression and activity of P-gp correlated significantly (p = .0031).
  
  
  CONCLUSIONS
  Failure in pharmacotherapy with P-gp substrates in AN patients are probably neither caused by different P-gp expression nor activity levels.
authors.affiliation: Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Caroline Henrike
authors.initials: CH
authors.lastname: Storch
authors.forename: Christoph
authors.initials: C
authors.lastname: Nikendei
authors.forename: Sandra
authors.initials: S
authors.lastname: Schild
authors.forename: Walter Emil
authors.initials: WE
authors.lastname: Haefeli
authors.forename: Johanna
authors.initials: J
authors.lastname: Weiss
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herzog
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008657:Metabolic Clearance Rate / Q000235:genetics; D009000:Monocytes / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000493:pharmacokinetics / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011619:Psychotropic Drugs; D012333:RNA, Messenger