Document Detail


Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.
MedLine Citation:
PMID:  17922559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To characterise the interactions between tacrolimus and antiretroviral drug combinations in hepatitis C virus-HIV co-infected patients who had received a liver transplant.
DESIGN: An observational, open-label, multiple-dose, two-period, one-sequence design clinical trial in which patients received tacrolimus as an immunosuppressive therapy during the postoperative period and then had an antiretroviral drug regimen added. Tacrolimus pharmacokinetics were evaluated at steady state during these two periods.
METHODS: Fourteen patients participated in the study and seven participated in the intensified pharmacokinetic protocol. Patients were included if they had undergone liver transplantation for end-stage chronic hepatitis C, absence of opportunistic infection, a CD4 cell count of >150 cells/microL and an undetectable HIV plasma viral load (<50 copies/mL) under highly active antiretroviral therapy. During the posttransplantation period, the tacrolimus dose was adjusted according to blood concentrations. When liver function and the tacrolimus dose were stable, antiretroviral therapy was reintroduced.
RESULTS: When lopinavir/ritonavir were added to the tacrolimus regimen (seven patients), the tacrolimus dose was reduced by 99% to maintain the tacrolimus concentration within the therapeutic range. Only two patients were treated with nelfinavir, which led to a wide variation in inhibition of tacrolimus metabolism. When efavirenz (four patients) or a nucleoside analogue combination (one patient) was added, very little change in tacrolimus dosing was required.
CONCLUSION: The lopinavir/ritonavir combination markedly inhibited tacrolimus metabolism, whereas the effect of efavirenz was small. Tacrolimus dosing must be optimised according to therapeutic drug monitoring and the antiretroviral drug combination.
Authors:
Elina Teicher; Isabelle Vincent; Laurence Bonhomme-Faivre; Chadi Abbara; Aurélie Barrail; Alain Boissonnas; Jean-Charles Duclos-Vallée; Anne-Marie Taburet; Didier Samuel; Daniel Vittecoq
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Clinical pharmacokinetics     Volume:  46     ISSN:  0312-5963     ISO Abbreviation:  Clin Pharmacokinet     Publication Date:  2007  
Date Detail:
Created Date:  2007-10-09     Completed Date:  2008-02-05     Revised Date:  2014-02-06    
Medline Journal Info:
Nlm Unique ID:  7606849     Medline TA:  Clin Pharmacokinet     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  941-52     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antiretroviral Therapy, Highly Active*
Area Under Curve
Benzoxazines / blood,  pharmacokinetics,  therapeutic use
CD4 Lymphocyte Count
Dose-Response Relationship, Drug
Female
Graft Rejection / diagnosis
HIV / drug effects
HIV Infections / complications,  therapy*
Half-Life
Hepatitis C / complications,  therapy*
Humans
Liver Transplantation*
Lopinavir
Male
Middle Aged
Nelfinavir / blood,  pharmacokinetics,  therapeutic use
Pyrimidinones / blood,  pharmacokinetics,  therapeutic use
Ritonavir / blood,  pharmacokinetics,  therapeutic use
Tacrolimus / blood,  pharmacokinetics*,  therapeutic use
Viral Load / methods
Chemical
Reg. No./Substance:
0/Benzoxazines; 0/Pyrimidinones; 2494G1JF75/Lopinavir; HO3OGH5D7I/Nelfinavir; JE6H2O27P8/efavirenz; O3J8G9O825/Ritonavir; WM0HAQ4WNM/Tacrolimus

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


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