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.
Method: 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).
Conclusion: Failure in pharmacotherapy with P-gp substrates in AN patients are probably neither caused by different P-gp expression nor activity levels.
(c) 2008 by Wiley Periodicals, Inc.