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PI‐61
Author(s) -
Sekar V. J.,
Guzman S.,
De Pauw M.,
De Paepe E.,
Vangeneugden T.,
Hoetelmans R.,
Lefebvre E.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.082
Subject(s) - ritonavir , pharmacokinetics , tolerability , dysgeusia , pharmacology , crossover study , medicine , morning , evening , adverse effect , chemistry , human immunodeficiency virus (hiv) , viral load , immunology , antiretroviral therapy , physics , alternative medicine , pathology , astronomy , placebo
BACKGROUND TMC114 is a protease inhibitor (PI) that is highly potent against wild‐type and drug resistant HIV. TMC114, in combination with low‐dose ritonavir (TMC114/RTV), is in Phase III studies. METHODS This was an open‐label, randomized, 3‐way crossover study in 18 healthy subjects to investigate the pharmacokinetic (PK) interaction between repeated doses of clarithromycin (CLAR) and TMC114/RTV. In 3 sessions, subjects received TMC114/RTV 400/100 mg b.i.d. (Treatment A), 500 mg CLAR b.i.d. (Treatment B), and 500 mg CLAR b.i.d. and TMC114/RTV 400/100 mg b.i.d. (Treatment C). Treatments were administered for 6 days with an additional morning dose on Day 7. Treatment (Trt) C included an additional evening dose of TMC114/RTV on Day 7. PK profiles were obtained on Day 7; TMC114 and ritonavir in Trt A and C and CLAR and 14‐hydroxy‐CLAR in Trt B and C. Safety and tolerability were assessed. RESULTS Exposure (AUC12h) to CLAR increased by 57% while 14‐hydroxy‐CLAR reduced to undetectable concentrations when TMC114/r was co‐administered. Exposure to TMC114 decreased by 13% and exposure to RTV was unchanged when co‐administered with CLAR. Treatments including CLAR were associated with a higher incidence of dysgeusia, a known side effect of CLAR. The incidence of other adverse events was similar between treatments. CONCLUSIONS No dose adjustments are necessary for subjects with normal renal function. For subjects with renal impairment, the recommendations in the CLAR U.S. package insert should be considered. Clinical Pharmacology & Therapeutics (2005) 79 , P23–P23; doi: 10.1016/j.clpt.2005.12.082