title: Pharmacokinetic parameters of once-daily rilpivirine following administration of efavirenz in healthy subjects.
abstract: BACKGROUND
  Rilpivirine and efavirenz share metabolic pathways (CYP3A), potentially leading to drug-drug interactions. We report the pharmacokinetics, ex vivo antiviral activity and safety of rilpivirine, following efavirenz treatment.
  
  
  METHODS
  HIV-negative adults received in fixed sequence: treatment A (rilpivirine 25 mg once daily for 14 days, followed by a washout), treatment B (efavirenz 600 mg once daily for 14 days), immediately followed by treatment C (rilpivirine 25 mg once daily for 28 days). Rilpivirine pharmacokinetic profiles were determined on days 1 and 14 of treatment A and days 1, 14, 21 and 28 of treatment C. Ex vivo antiviral activity was measured in treatments A and C using an exploratory assay. Safety was evaluated throughout.
  
  
  RESULTS
  From days 1 to 21, higher mean rilpivirine exposure was observed with treatment A compared with treatment C. The area under the concentration-time curve (AUC(24 h)) least squares (LS) means ratio (90% CI) for treatment C versus treatment A was 0.54 (0.46, 0.64; Day 1), 0.82 (0.75, 0.89; Day 14) and 0.84 (0.74, 0.94; Day 21). By day 28 of treatment C, the main rilpivirine pharmacokinetic parameters were similar to day 14 of treatment A (AUC(24 h) LS means ratio [90% CI], 0.91 [0.82, 1.01]), except for the minimum plasma concentration. At each time point in treatment C, samples of >80% of subjects demonstrated similar ex vivo antiviral activity compared with treatment A. All adverse events were grade 1 or 2.
  
  
  CONCLUSIONS
  These results provide useful information supporting a clinical study evaluating HIV-1-positive subjects switching from efavirenz to rilpivirine.
authors.affiliation: Tibotec BVBA, Beerse, Belgium. HCrauwel@its.jnj.com
authors.forename: Herta
authors.initials: H
authors.lastname: Crauwels
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.forename: James
authors.initials: J
authors.lastname: Witek
authors.forename: David
authors.initials: D
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000008:administration & dosage*; D003521:Cyclopropanes; D005260:Female; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000068696:Rilpivirine; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine; C098320:efavirenz