Pharmacokinetic interaction between TMC114/ritonavir and tenofovir disoproxil fumarate in healthy volunteers.
OBJECTIVE
TMC114 is a new HIV protease inhibitor, used in combination with low-dose ritonavir (TMC114/r) as a pharmacokinetic enhancer. Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor. Both antiretrovirals show activity against wild-type and resistant HIV. An open-label crossover study was conducted in HIV - healthy volunteers to investigate the potential for a pharmacokinetic interaction between TMC114/r and tenofovir.


METHODS
Two groups, each of six volunteers, were evaluated in two consecutive sessions. In session 1, volunteers received TMC114/r (300/100 mg bid) for 7 days, followed by a wash-out period of at least 6 days. In session 2, volunteers received TMC114/r (300/100 mg bid) plus TDF (300 mg qd).


RESULTS
When TMC114/r and TDF were coadministered, tenofovir plasma concentrations (C(min) and C(max)), and area under the curve (AUC(24 h)) increased by 37%, 24% and 22%, respectively. When TDF and ritonavir were coadministered, TMC114 plasma C(min), C(max) and AUC(12 h) increased by 24%, 16% and 21%, respectively. There were no changes in the urinary excretion of unchanged tenofovir or TMC114 during coadministration. Administration of TMC114/r in HIV- healthy volunteers with or without TDF was well tolerated.


CONCLUSIONS
The interaction between TMC114/r and tenofovir is not clinically relevant and no dose adjustments are required when these drugs are coadministered.
Hoetelmans
Richard M W
RM
Tibotec BVBA, Mechelen, Belgium. rhoetelm@tibbe.jnj.com
Mariën
Kris
K
De Pauw
Martine
M
Hill
Andrew
A
Peeters
Monika
M
Sekar
Vanitha
V
De Doncker
Piet
P
Woodfall
Brian
B
Lefebvre
Eric
E
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D000068698:Tenofovir; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir