Does tenofovir influence efavirenz pharmacokinetics?
BACKGROUND
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).


CONCLUSIONS
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.
Rotger
Margalida
M
Institute of Microbiology, University Hospital, Lausanne, Switzerland.
Colombo
Sara
S
Furrer
Hansjakob
H
Décosterd
Laurent
L
Buclin
Thierry
T
Telenti
Amalio
A
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D048588:Benzoxazines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D013557:Switzerland; D000068698:Tenofovir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; D000225:Adenine; C098320:efavirenz