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
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
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 11:51
Last modification date
20/08/2019 16:12