title: Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial.
abstract: In the ANRS IPERGAY pre-exposure prophylaxis (PrEP) trial, a single dose of tenofovir disoproxil fumarate and emtricitabine was taken orally 2-24 h before sexual intercourse. A sub-study was conducted to assess the pharmacokinetics of tenofovir and emtricitabine in blood, saliva and rectal tissue following this initial oral intake.
  
  
  
  Plasma, PBMC, saliva and rectal tissue sampling was performed over 24 h in 12 seronegative men before enrolment in the ANRS IPERGAY trial, following a single dose of 600 mg tenofovir disoproxil fumarate/400 mg emtricitabine. Ex vivo HIV infectibility of rectal biopsies was also assessed.
  
  
  
  The median plasma Tmaxof tenofovir (median Cmax: 401 μg/L) and emtricitabine (median Cmax: 2868 μg/L) was obtained 1 h (range: 0.5-4) and 2 h (range: 1-4) after dosing, respectively. The median C24of tenofovir and emtricitabine was 40 and 63 μg/L, respectively. The median PBMC tenofovir diphosphate and emtricitabine triphosphate levels were 12.2 and 16.7 fmol/106cells and 2800 and 2000 fmol/106cells at 2 and 24 h after dosing, respectively. Saliva/plasma AUC0-24ratios were 2% and 17% for tenofovir and emtricitabine, respectively. Emtricitabine was detected in rectal tissue 30 min after dosing, whereas tenofovir was only detectable at 24 h. Ex vivo HIV infectibility assays of rectal biopsies showed partial protection after dosing (P < 0.07).
  
  
  
  A single high dose of oral tenofovir disoproxil fumarate/emtricitabine provides rapid and high blood levels of tenofovir and emtricitabine, with rapid diffusion of emtricitabine in saliva and rectal tissue.
authors.affiliation: Department of Biochemistry, AP-HP, Hôpital Saint-Louis, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Fonsart
authors.affiliation: INSERM U941, Paris, France.
authors.forename: Sentob
authors.initials: S
authors.lastname: Saragosti
authors.affiliation: Department of Infectious Diseases, Hôpital Saint-Louis, AP-HP and University of Paris Diderot, Paris Sorbonne Cité, France.
authors.forename: Milad
authors.initials: M
authors.lastname: Taouk
authors.affiliation: Department of Pharmacology, Hôpital Bichat Claude Bernard, Paris, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.affiliation: University of Colorado, Denver, CO, USA.
authors.forename: Lane
authors.initials: L
authors.lastname: Bushman
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Charreau
authors.affiliation: INSERM U941, Paris, France.
authors.forename: Allan
authors.initials: A
authors.lastname: Hance
authors.affiliation: Department of Pharmacology, AP-HP, Hôpital Saint-Louis, Paris, France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Goldwirt
authors.affiliation: AIDES, Pantin, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Morel
authors.affiliation: INSERM U941, Paris, France.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mammano
authors.affiliation: Department of Infectious Diseases, Hôpital Saint-Louis, AP-HP and University of Paris Diderot, Paris Sorbonne Cité, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Loze
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Capitant
authors.affiliation: INSERM U941, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Clavel
authors.affiliation: Department of Virology, AP-HP, Hôpital Saint-Louis, University of Paris Diderot, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mahjoub
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: University of Colorado, Denver, CO, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
authors.affiliation: INSERM U941, Paris, France.|Department of Virology, AP-HP, Hôpital Saint-Louis, University of Paris Diderot, Paris, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.affiliation: INSERM U941, Paris, France jean-michel.molina@aphp.fr.|Department of Infectious Diseases, Hôpital Saint-Louis, AP-HP and University of Paris Diderot, Paris Sorbonne Cité, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis / Q000379:methods*; D000068679:Emtricitabine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D008297:Male; D010919:Placebos / Q000494:pharmacology; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D012463:Saliva / Q000737:chemistry*; D000068698:Tenofovir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D047568:Unsafe Sex
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D000068698:Tenofovir; D000068679:Emtricitabine