Expression and activity of P-glycoprotein (MDR1/ABCB1) in peripheral blood mononuclear cells from patients with anorexia nervosa compared with healthy controls.
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.
Storch
Caroline Henrike
CH
Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, D-69120 Heidelberg, Germany.
Nikendei
Christoph
C
Schild
Sandra
S
Haefeli
Walter Emil
WE
Weiss
Johanna
J
Herzog
Wolfgang
W
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
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