title: Pharmacokinetics and pharmacodynamics of the non-nucleoside reverse-transcriptase inhibitor etravirine in treatment-experienced HIV-1-infected patients.
abstract: The pharmacokinetics and pharmacodynamics of the antiretroviral agent etravirine were evaluated in two phase III clinical trials. Pharmacokinetic data were available in 577 patients randomized to receive etravirine. The mean (SD) population-pharmacokinetics-derived area under the concentration-time curve at 12 h (AUC(12 h)) and concentration at 0 h (C(0 h)) were 5,501 (4,544) ng·h/ml and 393 (378) ng/ml, respectively. Hepatitis C coinfection raised etravarine exposure, and concomitant use of tenofovir disoproxil fumarate lowered etravirine exposure, but these changes were not considered clinically relevant. Etravirine apparent oral clearance was not affected by age, weight, sex, race, hepatitis B coinfection status, creatinine clearance, or concomitant use of enfuvirtide. Virologic response (<50 copies/ml) at week 24 was 59% in patients randomized to etravirine vs. 41% in those receiving placebo (P < 0.0001). There was no apparent relationship between etravirine pharmacokinetics and either efficacy or safety. Factors other than the pharmacokinetics of etravirine such as the characteristics of the patients and the disease, as well as characteristics of the treatment regimen, predict virologic response.
authors.affiliation: Tibotec, Inc., Titusville, New Jersey, USA. tkakuda@its.jnj.com
authors.forename: T N
authors.initials: TN
authors.lastname: Kakuda
authors.forename: J R
authors.initials: JR
authors.lastname: Wade
authors.forename: E
authors.initials: E
authors.lastname: Snoeck
authors.forename: P
authors.initials: P
authors.lastname: Vis
authors.forename: M
authors.initials: M
authors.lastname: Schöller-Gyüre
authors.forename: M P
authors.initials: MP
authors.lastname: Peeters
authors.forename: C
authors.initials: C
authors.lastname: Corbett
authors.forename: S
authors.initials: S
authors.lastname: Nijs
authors.forename: J
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: L
authors.initials: L
authors.lastname: Leopold
authors.forename: G
authors.initials: G
authors.lastname: De Smedt
authors.forename: B J
authors.initials: BJ
authors.lastname: Woodfall
authors.forename: R M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000069454:Darunavir; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D063065:Organophosphonates / Q000008:administration & dosage; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D009570:Nitriles; D063065:Organophosphonates; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; C451734:etravirine; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir; D000069454:Darunavir