Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers.
OBJECTIVE
Two open-label, randomized, cross-over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.


METHODS
Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co-administration of etravirine with tenofovir disoproxil fumarate on either days 1-8 or days 9-16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.


RESULTS
The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration-time curve from 0 to 12 h (AUC(12 h)) for etravirine co-administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61-0.79) and 0.81 (0.75-0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC(24 h) was 1.16 (1.09-1.23) in Study 1 and 1.15 (1.09-1.21) in Study 2.


CONCLUSIONS
These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co-administered.
Kakuda
T N
TN
Tibotec Inc., Yardley, PA, USA. tkakuda@tibus.jnj.com
Schöller-Gyüre
M
M
De Smedt
G
G
Beets
G
G
Aharchi
F
F
Peeters
M P
MP
Vandermeulen
K
K
Woodfall
B J
BJ
Hoetelmans
R M W
RM
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001530:Belgium; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009570:Nitriles; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011724:Pyridazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011743:Pyrimidines; D000068698:Tenofovir; D055815:Young Adult
D019380:Anti-HIV Agents; D009570:Nitriles; D063065:Organophosphonates; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; D000068698:Tenofovir; D000225:Adenine