Influence of tenofovir, nevirapine and efavirenz on ritonavir-boosted atazanavir pharmacokinetics in HIV-infected patients.
OBJECTIVE
The influence of nevirapine, efavirenz and tenofovir co-administration on ritonavir-boosted atazanavir pharmacokinetics was investigated in HIV (human immunodeficiency virus)-infected patients.


METHODS
A population pharmacokinetic analysis was performed in the context of therapeutic drug monitoring (87 patients, 121 samples).


RESULTS
A significant increase of atazanavir clearance (Cl/F) was found when either tenofovir (group B), efavirenz (group C), or nevirapine (group D) were co administered with atazanavir/ritonavir in comparison with patients treated with atazanavir/ritonavir and nucleoside reverse transcriptase inhibitors (group A): 6.24+/-0.36 l h(-1) (group A) versus 7.42+/-0.25 l h(-1) (group B) versus 9.60+/-0.27 l h(-1) (group C) versus 17.53+/-0.57 l h(-1) (group D) (P<0.001). However, the decrease of the mean trough plasma concentration of atazanavir was significant only in group D: 1.02+/-0.86 mg/l (group A) versus 0.21+/-013 mg/l (group D) (P<0.001).


CONCLUSIONS
The increase in atazanavir clearance when it is used in combination with nevirapine, efavirenz and/or tenofovir suggests that therapeutic drug monitoring of atazanavir should be performed in such circumstances.
Dailly
Eric
E
Clinical Pharmacology Department, Hôtel Dieu, 9 Quai Moncousu, 44093, Nantes, Cedex, France. eric.dailly@chu-nantes.fr
Tribut
Olivier
O
Tattevin
Pierre
P
Arvieux
Cédric
C
Perré
Philippe
P
Raffi
François
F
Jolliet
Pascale
P
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D003521:Cyclopropanes; D004347:Drug Interactions; D005260:Female; D006678:HIV / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D010078:Oxazines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D019829:Nevirapine; D000068698:Tenofovir; D000225:Adenine; C098320:efavirenz; D019438:Ritonavir