Pharmacokinetics of 852A, an imidazoquinoline Toll-like receptor 7-specific agonist, following intravenous, subcutaneous, and oral administrations in humans

J Clin Pharmacol. 2007 Aug;47(8):962-9. doi: 10.1177/0091270007303766.


852A is an imidazoquinoline Toll-like receptor 7 agonist undergoing evaluation for the systemic treatment of cancer. 852A was administered to 6 healthy subjects as 3 rising subcutaneous doses (0.5 to 1.0 to 2.0 mg), to 6 subjects as 3 oral doses (10.0 to 20.0 to 15.0 mg, the third dose being a de-escalation), and to 6 subjects as a 2.0-mg dose by the subcutaneous, intravenous, and oral routes in crossover fashion. The subcutaneous and intravenous doses were well tolerated. One subject withdrew following the 20.0-mg oral dose because of hypotension. The 2.0-mg subcutaneous dose had 80.5% +/- 12.8% (mean +/- SD) bioavailability and gave serum concentrations comparable to intravenous administration by 30 minutes. Linear kinetics and an interferon-alpha dose response were observed for the 3 subcutaneous doses. Serum concentrations following the 2.0-mg oral dose were always lower than those following the same intravenous dose, and the oral route had a bioavailability of 26.5% +/- 7.84%. Concentrations appeared to increase with oral dose; however, large variabilities in both the rate and extent of absorption were seen between individuals. Approximately 40% of an absorbed dose was excreted unchanged in the urine. Overall, the study suggests that subcutaneous administration may be an acceptable method to deliver 852A for systemic applications.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biological Availability
  • Cohort Studies
  • Cross-Over Studies
  • Drug Administration Routes
  • Female
  • Humans
  • Male
  • Middle Aged
  • Quinolines / administration & dosage
  • Quinolines / pharmacokinetics*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacokinetics*
  • Toll-Like Receptor 7 / agonists*


  • N-(4-(4-amino-2-ethyl-1H-imidazo(4,5c)quinolin-1-yl)butyl)methanesulfonamide
  • Quinolines
  • Sulfonamides
  • Toll-Like Receptor 7