Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone.
BACKGROUND
Etravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) active against NNRTI-resistant HIV, is an inducer of CYP3A4 and an inhibitor of CYP2C9/19.


METHODS
The effect of etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone was assessed in 30 HIV-negative females. Following a run-in cycle with ethinylestradiol/norethindrone, the pharmacokinetics of ethinylestradiol and norethindrone was assessed on Day 15 of Cycle 2. Etravirine 200 mg bid was coadministered on Day 1 to Day 15 of Cycle 3, with pharmacokinetic assessments of ethinylestradiol, norethindrone and etravirine on Day 15.


RESULTS
When combined with etravirine, the least-squares means (LSM) ratios (90% confidence interval) for ethinylestradiol AUC(24h), C(max) and C(min) were 1.22 (1.13-1.31), 1.33 (1.21-1.46) and 1.09 (1.01-1.18), respectively, compared to administration alone. LSM ratios for norethindrone parameters were 0.95 (0.90-0.99), 1.05 (0.98-1.12) and 0.78 (0.68-0.90), respectively.


CONCLUSIONS
These changes are not considered clinically relevant. No loss in contraceptive efficacy is expected when coadministered with etravirine.
Schöller-Gyüre
Monika
M
Research and Development, Tibotec BVBA, B-2800 Mechelen, Belgium. mscholle@its.jnj.com
Kakuda
Thomas N
TN
Woodfall
Brian
B
Aharchi
Fatima
F
Peeters
Monika
M
Vandermeulen
Kati
K
Hoetelmans
Richard M W
RM
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D009570:Nitriles; D009640:Norethindrone / Q000009:adverse effects / Q000493:pharmacokinetics*; D011724:Pyridazines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011743:Pyrimidines; D055815:Young Adult
D019380:Anti-HIV Agents; D003280:Contraceptives, Oral, Synthetic; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; D004997:Ethinyl Estradiol; D009640:Norethindrone