Document Detail

In vitro influence of fatty acids and bilirubin on binding of mycophenolic acid to human serum albumin.
MedLine Citation:
PMID:  20965681     Owner:  NLM     Status:  In-Process    
Mycophenolic acid (MPA) is 98-99% bound to albumin. Because MPA is restrictively cleared and has a low extraction coefficient, increase in its free fraction related to decreased albumin binding results in lower total concentrations but unchanged unbound concentrations. Multiple factors, including hypoalbuminemia, impaired renal function, and accumulated mycophenolic acid glucuronide are known to reduce MPA protein binding. Little is known about the influence of fatty acids and bilirubin on this issue. By using quenching fluorescence method, the aims of this study were to investigate in vitro the binding properties of MPA, then the influence of myristic acid and bilirubin on MPA binding to albumin. The estimate of dissociation constant (Kd) of MPA was 13.2 [CI 95 12.7-13.8] μM. In the presence of myristic acid (concentration range 4-100 μM), apparent Kd (Kd(app)) of MPA was approximately 1.5-10-fold greater. For myristic acid/albumin molar ratio reachable in clinical settings (2:1 and 5:1), Kd(app) of MPA rose about a factor 1.5 and 2.2, respectively. In the presence of bilirubin (concentration range 0.5-5 μM), Kd(app) of MPA was approximately 1.5-5-fold greater than MPA Kd. For bilirubin/albumin molar ratio reachable in clinical settings (1:4 and 1:2), Kd(app) of MPA rose about a factor 1.5 and 1.9, respectively. These data suggest that hypertriglyceridemia or cholestasis may significantly increase MPA free fraction in clinical settings, thereby lowering MPA total concentration in plasma while the free concentration remains unchanged. These results may help to optimize the therapeutic drug monitoring of MPA.
Yoann Vial; Michel Tod; Marilyne Hornecker; Saik Urien; Filomena Conti; Alain Dauphin; Yvon Calmus; Benoit Blanchet
Publication Detail:
Type:  Journal Article     Date:  2010-09-29
Journal Detail:
Title:  Journal of pharmaceutical and biomedical analysis     Volume:  54     ISSN:  1873-264X     ISO Abbreviation:  J Pharm Biomed Anal     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309336     Medline TA:  J Pharm Biomed Anal     Country:  England    
Other Details:
Languages:  eng     Pagination:  607-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Laboratoire de pharmacologie-toxicologie, service de Pharmacie, GH Cochin Saint Vincent de Paul, 75014 Paris, APHP, France.
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