Document Detail


Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients.
MedLine Citation:
PMID:  12099384     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Atorvastatin is increasingly used as a cholesterol-lowering agent in solid organ transplant recipients receiving cyclosporine A (CsA). However, the potential bilateral pharmacokinetic interaction between atorvastatin and CsA in renal transplant recipients has not previously been examined. Baseline 12-h CsA pharmacokinetic investigation was performed in 21 renal transplant recipients and repeated after 4 weeks of atorvastatin treatment (10 mg/ d). At week 4, 24-h pharmacokinetics of atorvastatin was also performed. All patients received basiliximab induction followed by CsA and prednisolone immunosuppression. Compared with historic controls, CsA-treated patients showed, on average, sixfold higher plasma HMG-CoA reductase inhibitory activity after 4 weeks of atorvastatin treatment (p < 0.05). Atorvastatin had a moderate effect on the pharmacokinetics of CsA and reduced the AUC0-12 (area under curve, 0-12h) by 9.5 +/- 18% (p = 0.013) and Cmax (maximal concentration) by 13.5 +/- 24% (p =0.009), while C12 (trough level) was unchanged (p =0.42). Total and LDL cholesterol decreased by 26.8 +/- 8.4% (p < 0.0001) and 41.5 +/- 11.0% (p < 0.0001), respectively. Bilateral pharmacokinetic interaction between atorvastatin and CsA resulted in sixfold higher plasma HMG-CoA reductase inhibitory activity, but only a moderate decrease in systemic exposure of CsA.
Authors:
A Asberg; A Hartmann; E Fjeldså; S Bergan; H Holdaas
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons     Volume:  1     ISSN:  1600-6135     ISO Abbreviation:  Am. J. Transplant.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2002-07-08     Completed Date:  2002-07-31     Revised Date:  2007-02-14    
Medline Journal Info:
Nlm Unique ID:  100968638     Medline TA:  Am J Transplant     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  382-6     Citation Subset:  IM    
Affiliation:
Medical Department, The National Hospital, Oslo, Norway. anderas@klinmed.uio.no
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antibodies, Monoclonal / therapeutic use
Area Under Curve
Cyclosporine / diagnostic use,  pharmacokinetics*
Drug Interactions
Female
Heptanoic Acids / diagnostic use,  pharmacokinetics*
Humans
Hydroxymethylglutaryl CoA Reductases / diagnostic use,  pharmacokinetics
Immunosuppressive Agents / diagnostic use,  pharmacokinetics
Kidney Transplantation / immunology*
Male
Middle Aged
Prednisolone / therapeutic use
Pyrroles / diagnostic use,  pharmacokinetics*
Recombinant Fusion Proteins*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Heptanoic Acids; 0/Immunosuppressive Agents; 0/Pyrroles; 0/Recombinant Fusion Proteins; 0/basiliximab; 110862-48-1/atorvastatin; 50-24-8/Prednisolone; 59865-13-3/Cyclosporine; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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