Pharmacokinetics of once-daily etravirine without and with once-daily darunavir/ritonavir in antiretroviral-naive HIV type-1-infected adults.
BACKGROUND
A pharmacokinetic trial was conducted to evaluate the potential for once-daily etravirine in antiretroviral regimens without and with darunavir/ritonavir.


METHODS
During this multicentre, open-label, Phase IIa trial, treatment-naive patients aged > or =18 years with HIV type-1 (HIV-1) received etravirine 400 mg once daily with tenofovir disoproxil fumarate/emtricitabine 300/200 mg once daily from days 1-14; on days 15-28, darunavir/ritonavir 800/100 mg once daily was added. On day 29, etravirine was discontinued and patients continued with the other medications to day 42. Serial blood sampling for etravirine pharmacokinetics was performed over 24 h on day 14 and 28; patients fasted for > or =10 h prior to these visits.


RESULTS
Of 23 enrolled patients (male 87%, Caucasian 39%), pharmacokinetic profiles for etravirine were available for 21 and 20 patients on day 14 and 28, respectively. The plasma concentration-time profile and pharmacokinetics for etravirine were unchanged with or without darunavir/ritonavir. The mean maximum plasma concentration (C(max)) was reached 4 h after administration and was 790 and 801 ng/ml on day 14 and 28, respectively; mean area under the plasma concentration-time curve (AUC) from before administration to 24 h after administration was 10,410 ng*h/ml on day 14 and 10,720 ng*h/ml on day 28. In a post-hoc analysis, etravirine C(max) was higher, minimum plasma concentration was lower and AUC was similar when compared with etravirine 200 mg twice daily.


CONCLUSIONS
Addition of darunavir/ritonavir to etravirine, all dosed once daily, did not have a clinically significant effect on the pharmacokinetics of etravirine. Findings support further investigation of etravirine 400 mg once daily in HIV-1-infected patients. (Trial registration number NCT00534352.).
DeJesus
Edwin
E
Orlando Immunology Center, Orlando, FL, USA. edejesus@oicorlando.com
Lalezari
Jacob P
JP
Osiyemi
Olayemi O
OO
Ruane
Peter J
PJ
Ryan
Robert
R
Kakuda
Thomas N
TN
Witek
James
J
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000069454:Darunavir; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D009570:Nitriles; D063065:Organophosphonates / Q000008:administration & dosage; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D000068698:Tenofovir; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D009570:Nitriles; D063065:Organophosphonates; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C451734:etravirine; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir; D000069454:Darunavir