Document Detail

A comparison of the effect of ciclosporin and sirolimus on the pharmokinetics of mycophenolate in renal transplant patients.
MedLine Citation:
PMID:  16995869     Owner:  NLM     Status:  MEDLINE    
AIM: To compare the pharmacokinetics of mycophenolic acid when given with either ciclosporin or sirolimus, and investigate in vitro the potential effect of ciclosporin, sirolimus, tacrolimus and everolimus on mycophenolic acid metabolism.
METHODS: In renal transplant patients given mycophenolate mofetil in combination with ciclosporin (n = 19) or sirolimus (n = 12), concentration-time profiles of mycophenolic acid, mycophenolic-acid-phenyl-glucuronide, mycophenolic-acid-acyl-glucuronide and mycophenolic-acid-phenyl-glucoside were determined at one month post-transplant. The effect of immunosuppressive drugs on mycophenolic acid glucuronidation and glycosylation was investigated in vitro using human liver microsomes.
RESULTS: The mean mycophenolic acid AUC(0-9 h) in the sirolimus group was 44.9 mg h(-1) L(-1) (95% CI: 34.7-55.1), vs. 30.5 mg h(-1) L(-1) (95% CI: 25.4-35.6) in the ciclosporin group, corresponding to 1.5-fold dose-normalized difference (95% CI: 1.1-1.9; P < 0.05). In addition, the metabolite/mycophenolic acid AUC(0-9 h) ratios were significantly higher in patients cotreated with ciclosporin than with sirolimus, giving values of 1.8-fold (95% CI: 1.3-2.3; P = 0.0009), 2.6-fold (95% CI: 2.0-3.3; P < 0.0001) and 4.3-fold (95% CI: 2.6-6.0; P = 0.0016) for mycophenolic-acid-phenyl-glucuronide, mycophenolic-acid-acyl-glucuronide and mycophenolic-acid-phenyl-glucoside, respectively. In vitro, none of the immunosuppressive drugs tested inhibited mycophenolic acid metabolism.
CONCLUSION: Patients taking mycophenolate mofetil and sirolimus experience a higher exposure to mycophenolic acid and a lower exposure to mycophenolic acid metabolites than those being treated with mycophenolate mofetil and ciclosporin. This interaction is probably not caused by inhibition of mycophenolic acid glucuronidation or glycosylation, but is more likely to be due to the influence of ciclosporin on the excretion of mycophenolic acid metabolites into bile.
Nicolas Picard; Aurélie Prémaud; Annick Rousseau; Yannick Le Meur; Pierre Marquet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  62     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-25     Completed Date:  2007-03-29     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  477-84     Citation Subset:  IM    
Laboratory of Pharmacology, Faculty of Medicine, University of Limoges, France.
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MeSH Terms
Cyclosporine / pharmacology*,  therapeutic use
Drug Interactions
Immunosuppressive Agents / pharmacokinetics*,  therapeutic use
Kidney Transplantation*
Middle Aged
Mycophenolic Acid / analogs & derivatives*,  pharmacokinetics,  therapeutic use
Sirolimus / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Immunosuppressive Agents; 24280-93-1/Mycophenolic Acid; 53123-88-9/Sirolimus; 59865-13-3/Cyclosporine; 9242ECW6R0/mycophenolate mofetil

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