title: Steady-state pharmacokinetics of rilpivirine under different meal conditions in HIV-1-infected Ugandan adults.
abstract: OBJECTIVE
  To investigate the effect of food on the steady-state pharmacokinetics of rilpivirine when administered as a fixed-dose combination tablet containing tenofovir disoproxil fumarate, emtricitabine plus rilpivirine (TDF/FTC/RPV) in HIV-1-infected Ugandan patients.
  
  
  METHODS
  This was an open-label, three-period, longitudinal pharmacokinetic study with patients serving as their own controls. Fifteen consenting and virologically suppressed HIV-1-infected adults were switched from an efavirenz-based regimen to TDF/FTC/RPV for 56 days. Enrolled patients underwent 24 h blood sampling with TDF/FTC/RPV dosing in the fasted state (day 42), with a low-fat meal (11 g of fat/353 kcal, day 49) and with a moderate-fat meal (19 g of fat/589 kcal, day 56; reference). A viral load assessment was performed on day 56.
  
  
  RESULTS
  Rilpivirine AUC0-24 was significantly decreased by 16% (geometric mean ratio, 90% CI: 0.84, 0.73-0.96) during administration in the fasted state when compared with AUC0-24 during administration with a moderate-fat meal. Similarly, rilpivirine C24 was significantly decreased by 21% (0.79, 0.65-0.97) in the fasted state compared with a moderate-fat meal. Pharmacokinetic parameters were unchanged during administration with a low-fat meal, except for C24, which was significantly increased by 15% (1.15, 1.01-1.31) when compared with the moderate-fat meal. Rilpivirine Cmax was similar under the three meal conditions. Virological suppression was unchanged at the end of the study.
  
  
  CONCLUSIONS
  A food effect was observed for steady-state pharmacokinetic parameters of rilpivirine (AUC0-24 and C24) when TDF/FTC/RPV was administered in the fasted state compared with the moderate-fat meal. The TDF/FTC/RPV formulation can be administered with either a low-fat or moderate-fat meal.
authors: Infectious Diseases Institute, Makerere University, Kampala, Uganda mlamorde@idi.co.ug.
authors: Mohammed
authors: M
authors: Lamorde
authors: Infectious Diseases Institute, Makerere University, Kampala, Uganda.
authors: Stephen
authors: S
authors: Walimbwa
authors: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors: Pauline
authors: P
authors: Byakika-Kibwika
authors: Infectious Diseases Institute, Makerere University, Kampala, Uganda.
authors: Michael
authors: M
authors: Katwere
authors: Infectious Diseases Institute, Makerere University, Kampala, Uganda.
authors: Lillian
authors: L
authors: Mukisa
authors: Infectious Diseases Institute, Makerere University, Kampala, Uganda.
authors: Joseph B
authors: JB
authors: Sempa
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors: Laura
authors: L
authors: Else
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors: David J
authors: DJ
authors: Back
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors: Saye H
authors: SH
authors: Khoo
authors: Department of Global Health, Northwestern University, Chicago, IL, USA Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin, Ireland GUIDE Clinic, St James's Hospital, Dublin, Ireland.
authors: Concepta
authors: C
authors: Merry
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004032:Diet / Q000379:methods*; D004338:Drug Combinations; D000068679:Emtricitabine / Q000008:administration & dosage; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D000068696:Rilpivirine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068698:Tenofovir / Q000008:administration & dosage; D014454:Uganda; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D000068698:Tenofovir; D000068696:Rilpivirine; D000068679:Emtricitabine
keywords: Complera; food–drug interactions; sub-Saharan Africa