PMID- 19195326
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20210826
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 13
IP  - 8
DP  - 2008
TI  - Pharmacokinetics of elvitegravir and etravirine following coadministration of 
      ritonavir-boosted elvitegravir and etravirine.
PG  - 1011-7
AB  - BACKGROUND: This crossover, open-label clinical study evaluated the potential for 
      clinically relevant drug interactions between ritonavir-boosted elvitegravir 
      (elvitegravir/r), an HIV integrase inhibitor, and etravirine, a non-nucleoside 
      reverse transcriptase inhibitor. METHODS: Healthy volunteers were randomized into 
      one of two groups, each with two arms. Group 1 (n = 20) followed a sequence of 
      10-day dosing of elvitegravir/r (150/100 mg once daily) and elvitegravir/r plus 
      etravirine (200 mg twice daily) or the reverse (n = 10 per sequence). Group 2 (n 
      = 14) followed a sequence of 10-day dosing of etravirine and etravirine plus 
      elvitegravir/r or the reverse (n = 7 per sequence), all under fed conditions. 
      Elvitegravir, ritonavir and etravirine pharmacokinetics were determined on days 
      10 and 20 using non-compartmental analyses. Lack of pharmacokinetic alteration 
      bounds for 90% confidence intervals (CI) about the geometric mean ratio (GMR; 
      coadministration versus alone) were 70-143% for elvitegravir and ritonavir 
      pharmacokinetics (maximum concentration [C(max)], concentration at the end of the 
      dosing interval [C(tau)] and area under the plasma concentration-time curve 
      [AUC(tau); 0-24 h] and 80-125% for etravirine pharmacokinetics (AUC(tau) 0-12 h). 
      RESULTS: Of the 34 enrolled participants, 31 completed the study. There were 
      three discontinuations, but none were caused by adverse events (AEs). The most 
      common treatment-emergent AE was headache. Elvitegravir pharmacokinetic GMR was 
      6-7% higher following elvitegravir/r plus etravirine dosing versus 
      elvitegravir/r. The GMR for etravirine and ritonavir AUC(tau) were 2.4% and 12.3% 
      lower, respectively. Importantly, the 90% CI for elvitegravir and etravirine 
      pharmacokinetics and AUC(tau) and C(max) for ritonavir were within the lack of 
      alteration bounds. CONCLUSIONS: Elvitegravir/r and etravirine do not undergo 
      clinically relevant drug interactions and can be coadministered without dose 
      adjustment.
FAU - Ramanathan, Srinivasan
AU  - Ramanathan S
AD  - Gilead Sciences, Inc., Foster City, CA, USA. sramanathan@gilead.com
FAU - Kakuda, Thomas N
AU  - Kakuda TN
FAU - Mack, Rebecca
AU  - Mack R
FAU - West, Steve
AU  - West S
FAU - Kearney, Brian P
AU  - Kearney BP
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (HIV Protease Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (Pyridazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Quinolones)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0C50HW4FO1 (etravirine)
RN  - 4GDQ854U53 (elvitegravir)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cross-Over Studies
MH  - Drug Therapy, Combination
MH  - Female
MH  - HIV Protease Inhibitors/administration & dosage/*pharmacokinetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles
MH  - Pyridazines/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Pyrimidines
MH  - Quinolones/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Reverse Transcriptase Inhibitors/administration & dosage/*pharmacokinetics
MH  - Ritonavir/*administration & dosage/adverse effects
EDAT- 2009/02/07 09:00
MHDA- 2009/04/09 09:00
CRDT- 2009/02/07 09:00
PHST- 2009/02/07 09:00 [entrez]
PHST- 2009/02/07 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PST - ppublish
SO  - Antivir Ther. 2008;13(8):1011-7.