| The impact of everolimus versus mycophenolate on blood and lymphocyte cyclosporine exposure in heart-transplant recipients. | |
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MedLine Citation:
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PMID: 19458944 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Trough- or 2-h post-dose (C2) blood cyclosporine (CsA) concentrations are used for prediction of efficacy and toxicity of CsA in transplant recipients concomitantly treated with antiproliferative agents, but information on utility of blood CsA levels in patients treated with proliferation signal inhibitors (PSIs), such as everolimus, is sparse. Because of the inhibitory effect of PSIs on the P-glycoprotein drug efflux pump present in lymphocytes, we hypothesized that CsA pharmacokinetics in blood and lymphocytes were dissociated in patients concomitantly treated with everolimus. METHODS: Twelve-hour pharmacokinetic studies of whole-blood and intralymphocytic CsA concentrations were conducted in long-term heart-transplant recipients treated with mycophenolate mofetil (MMF) + CsA (n = 8) and everolimus + CsA (n = 9). RESULTS: There was a highly significant correlation between blood CsA C2 levels and blood CsA AUC(0-12) in groups of patients treated with MMF or everolimus (R(2) 0.93 and 0.96, respectively; P < 0.001 for both). Whereas blood CsA C2 levels were closely associated with lymphocyte CsA AUC(0-12) in patients treated with MMF (R(2) = 0.98), there was poor correlation between whole-blood C2 and lymphocyte AUC(0-12) in patients treated with everolimus (R(2) = 0.24). CONCLUSION: Standard blood CsA levels accurately predict intralymphocytic exposure to CsA in patients concomitantly treated with MMF but not in patients treated with everolimus. |
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Authors:
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Finn Gustafsson; David Barth; Diego H Delgado; Meerna Nsouli; Jill Sheedy; Heather J Ross |
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Publication Detail:
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Type: Clinical Trial; Journal Article Date: 2009-05-21 |
Journal Detail:
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Title: European journal of clinical pharmacology Volume: 65 ISSN: 1432-1041 ISO Abbreviation: Eur. J. Clin. Pharmacol. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-09 Completed Date: 2009-08-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1256165 Medline TA: Eur J Clin Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 659-65 Citation Subset: IM |
Affiliation:
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Heart Failure and Transplant, Division of Cardiology, University Health Network, Toronto General Hospital, Toronto, ON, Canada. finng@dadlnet.dk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Cyclosporine / blood, therapeutic use* Dose-Response Relationship, Drug Female Heart Transplantation / immunology*, physiology Humans Immunosuppressive Agents / blood, therapeutic use* Lymphocytes / immunology Male Middle Aged Mycophenolic Acid / analogs & derivatives*, blood, therapeutic use Sirolimus / analogs & derivatives*, blood, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Immunosuppressive Agents; 128794-94-5/mycophenolate mofetil; 159351-69-6/everolimus; 24280-93-1/Mycophenolic Acid; 53123-88-9/Sirolimus; 59865-13-3/Cyclosporine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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