Document Detail


Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end-stage renal disease and transplant patients: a pilot study.
MedLine Citation:
PMID:  18482049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Promising data regarding the safety and efficacy of gastric bypass surgery (GBS) as an option to address obesity in the transplant population are emerging. The data lack on how GBS may alter the pharmacokinetics (PK) of modern immunosuppression. The objective of this study was to describe the alterations in the PK of modern immunosuppressants and the GBS population.
METHODS: Data are presented on six subjects who participated in this trial--four were on dialysis and two were renal transplant recipients. Dialysis-dependent bypass subjects received a single dose of 6 mg of sirolimus, two 4-mg doses of tacrolimus and two 1000-mg doses of mycophenolate mofetil (MMF) over the 24-h study period. Transplant recipients continued their current regimen. Maximum plasma concentration (C(max)), time to reach the maximum plasma concentration (T(max)) and the area under the plasma concentration vs. time curve (AUC(0-12) and AUC(0-infinity) where appropriate) were calculated for tacrolimus, sirolimus, mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG).
RESULTS: Significant inter-patient variability in the C(max), T(max) and AUC of tacrolimus, sirolimus MPA and MPAG was observed. A notable difference in the AUC:dose ratio for tacrolimus was seen when comparing data with published data in the non-bypass population. Similar differences in PK were seen with sirolimus, MPA and MPAG.
CONCLUSIONS: When comparing the PK of sirolimus, tacrolimus, MPA and MPAG to published PK data in the non-bypass population, significant differences are observed. It is likely that transplant recipients with GBS would need higher doses of tacrolimus, sirolimus and MMF to provide similar exposure to a non-bypass patient.
Authors:
Christin C Rogers; Rita R Alloway; J Wesley Alexander; Michael Cardi; Jennifer Trofe; Alexander A Vinks
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical transplantation     Volume:  22     ISSN:  1399-0012     ISO Abbreviation:  Clin Transplant     Publication Date:    2008 May-Jun
Date Detail:
Created Date:  2008-05-16     Completed Date:  2008-07-21     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  8710240     Medline TA:  Clin Transplant     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  281-91     Citation Subset:  IM    
Affiliation:
University of Cincinnati, Department of Surgery, Cincinnati, OH 45267-0585, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Gastric Bypass*
Glucuronides / pharmacokinetics
Humans
Immunosuppressive Agents / pharmacokinetics*
Kidney Failure, Chronic / metabolism*
Kidney Transplantation*
Middle Aged
Mycophenolic Acid / administration & dosage,  analogs & derivatives,  pharmacokinetics*
Pilot Projects
Renal Dialysis
Sirolimus / administration & dosage,  pharmacokinetics*
Tacrolimus / administration & dosage,  pharmacokinetics*
Grant Support
ID/Acronym/Agency:
K24 HD050387-03/HD/NICHD NIH HHS; U10 HD037249-10/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Glucuronides; 0/Immunosuppressive Agents; 0/mycophenolic acid glucuronide; 109581-93-3/Tacrolimus; 24280-93-1/Mycophenolic Acid; 53123-88-9/Sirolimus

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


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