Does tenofovir influence efavirenz pharmacokinetics?

Details

Serval ID
serval:BIB_A7D2AFCBBA6A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Does tenofovir influence efavirenz pharmacokinetics?
Journal
Antiviral Therapy
Author(s)
Rotger  M., Colombo  S., Furrer  H., Decosterd  L., Buclin  T., Telenti  A.
ISSN
1359-6535 (Print)
Publication state
Published
Issued date
2007
Volume
12
Number
1
Pages
115-8
Notes
Journal Article
Research Support, Non-U.S. Gov't
Abstract
INTRODUCTION: A recent report described a possible interaction between tenofovir (TFV) and efavirenz (EFV). Patients developed neuropsychiatric manifestations upon introduction of TFV on a stable EFV-containing regimen. We evaluated the possibility of a pharmacokinetic interaction between TFV and EFV by assessing cross-sectional and longitudinal data in 169 individuals receiving EFV. RESULTS: EFV plasma area-under-the-curve (AUC) levels were comparable among individuals receiving (n=18) or not receiving TFV (n=151); 57,962 versus 52,293 ng*h/ml. However, under conditions of limited EFV metabolism, that is, the group of 23 individuals carrying two copies of CYP2B6 loss/diminished-function alleles, plasma AUC values were highest among individuals receiving TFV (n=5, 353,031 ng*h/ml), compared with those not receiving TFV (n=18, 180,689 ng*h/ml). Statistical analysis identified both a global, sixfold effect of CYP2B6 loss/diminished function (P < 0.0001) and a significant interaction between the number of loss/diminished-function alleles and the co-medication with TFV (P = 0.009). CONCLUSION: Although there is no clear evidence for a pharmacokinetic interaction between TFV and EFV, we cannot rule out an interaction between these drugs restricted to individuals who are slow EFV metabolizers.
Keywords
Adenine/*analogs & derivatives/pharmacology/therapeutic use Adult Anti-HIV Agents/pharmacokinetics/*pharmacology/therapeutic use Area Under Curve Aryl Hydrocarbon Hydroxylases/genetics/metabolism Benzoxazines/blood/*pharmacokinetics/therapeutic use Cross-Sectional Studies Drug Interactions Drug Therapy, Combination Female Genotype HIV Infections/drug therapy/*metabolism Humans Liver/enzymology Longitudinal Studies Male Middle Aged Models, Biological Oxidoreductases, N-Demethylating/genetics/metabolism Phenotype Phosphonic Acids/*pharmacology/therapeutic use Reverse Transcriptase Inhibitors/pharmacokinetics/*pharmacology/therapeutic use Switzerland
Pubmed
Web of science
Create date
25/01/2008 10:51
Last modification date
20/08/2019 15:12
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