Pharmacokinetics of a weekly transdermal delivery system of tenofovir alafenamide in hairless rats

Int J Pharm. 2020 May 30:582:119342. doi: 10.1016/j.ijpharm.2020.119342. Epub 2020 Apr 18.


Tenofovir alafenamide (TAF) is a potent prodrug of tenofovir (TFV) for HIV prophylaxis, and HIV and HBV treatment. Compared to oral daily doses, transdermal administration of TAF may be more advantageous for long-term adherence by offering sustained drug delivery and reduced dosing frequency. Here, we described the plasma pharmacokinetics (PK) of an optimized once-weekly suspension transdermal delivery system (TDS) for TAF (96 mg/25 cm2 of TDS) in female hairless rats. Over the study period, the TAF TDS delivered an overall low level of TAF (median: 1.43 [0.02-3.28] ng/mL) and a sustained level of the stable metabolite and parent drug, TFV. Relative to the projected exposure corresponding to six-day oral daily doses, a comparable TAF exposure but a substantially lower TFV exposure was resulted from the TAF TDS, suggesting a lower risk of TFV-associated adverse effects. TAF, TFV, and phosphorylated TFVs (TFV-monophosphate and diphosphate) were found distributed in vaginal tissue, the portal of entry for HIV during male-to-female sexual transmission. Skin adhesion and tolerance were acceptable given the animal model used. PK evaluation of the TAF TDS in hairless rats demonstrates the proof of concept that transdermal delivery can be an alternative route for a sustained, once-weekly systemic delivery of TAF.

Keywords: Antiretroviral drug; Pharmacokinetics; Sustained delivery; Tenofovir alafenamide (TAF); Transdermal delivery system (TDS); Transdermal drug delivery.

Publication types

  • Comparative Study

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / blood
  • Adenine / pharmacokinetics
  • Adenine / toxicity
  • Administration, Cutaneous
  • Administration, Oral
  • Alanine
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / toxicity
  • Delayed-Action Preparations
  • Drug Administration Schedule
  • Drug Compounding
  • Female
  • Injections, Intravenous
  • Proof of Concept Study
  • Rats, Hairless
  • Tenofovir / analogs & derivatives
  • Tissue Distribution
  • Transdermal Patch
  • Vagina / metabolism


  • Antiviral Agents
  • Delayed-Action Preparations
  • Tenofovir
  • tenofovir alafenamide
  • Adenine
  • Alanine