Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Harrison, L.I. et al.

Lester I. Harrison, Calvin Astry, Sandeep Kumar, Carla Yunis,

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

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.[1]

References

Pharmacokinetics of 852A, an imidazoquinoline Toll-like receptor 7-specific agonist, following intravenous, subcutaneous, and oral administrations in humans. Harrison, L.I., Astry, C., Kumar, S., Yunis, C. J. Clin. Pharmacol (2007) [Pubmed]

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