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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 11/2007

01-11-2007 | Original Research Article

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

Authors: Elina Teicher, Isabelle Vincent, Laurence Bonhomme-Faivre, Chadi Abbara, Aurélie Barrail, Alain Boissonnas, Jean-Charles Duclos-Vallée, Dr Anne-Marie Taburet, Didier Samuel, Daniel Vittecoq

Published in: Clinical Pharmacokinetics | Issue 11/2007

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Abstract

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/μL 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.
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Metadata
Title
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
Authors
Elina Teicher
Isabelle Vincent
Laurence Bonhomme-Faivre
Chadi Abbara
Aurélie Barrail
Alain Boissonnas
Jean-Charles Duclos-Vallée
Dr Anne-Marie Taburet
Didier Samuel
Daniel Vittecoq
Publication date
01-11-2007
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 11/2007
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200746110-00002