Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers.
BACKGROUND
This open-label, crossover study investigated the pharmacokinetic interaction between TMC114 (darunavir [Prezista]), administered with low-dose ritonavir (TMC114/r) and efavirenz (EFV) in HIV-negative, healthy volunteers.


METHODS
Volunteers received TMC114/r 300/100 mg twice daily for 6 days, and once daily on day 7 (session 1). After a 7-day washout period volunteers received EFV 600 mg once daily for 18 days (session 2), with coadministration of TMC114/r 300/100 mg twice daily from day 11-day 16 and TMC114/r once daily on day 17.


RESULTS
When coadministered with TMC114/r, plasma concentrations of EFV were slightly increased. In the presence of TMC114/r, EFV minimum (Cmin) and maximum (Cmax) plasma concentrations increased by 15-17%, and by 21% for EFV area under the curve (AUC24h). TMC114/r and EFV coadministration resulted in TMC114 Cmin, Cmax and AUC12h decreases of 31%, 15% and 13%, respectively. No serious adverse events (AEs) or AEs leading to withdrawal were reported in this trial. Overall, TMC114/r and EFV coadministration was well tolerated.


CONCLUSIONS
The clinical significance of the changes in AUC and Cmin seen with TMC114/r and EFV coadministration has not been established; this combination should be used with caution. Similar findings are expected with the approved TMC114/r 600/100 mg twice daily dose.
Sekar
Vanitha J
VJ
Tibotec, Inc., Yardley, PA, USA. vsekar@tibus.jnj.com
De Pauw
Martine
M
Mariën
Kris
K
Peeters
Monika
M
Lefebvre
Eric
E
Hoetelmans
Richard M W
RM
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D000069454:Darunavir; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D018023:HIV Seronegativity; D006801:Humans; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014838:Volunteers
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C098320:efavirenz; D019438:Ritonavir; D000069454:Darunavir