Background/aims: To explore safety, pharmacokinetics, and pharmacodynamics of oral administration of resiquimod, a Toll-like receptor 7 and 8 agonist that induces endogenous interferon-alpha, in subjects with chronic hepatitis C virus infection VSports手机版. .

Methods: Two randomized, double-blind phase IIa studies of resiquimod administered two times per week for 4 weeks. Multicenter study (U. S. ): 12 subjects received resiquimod 0. 01 mg/kg and 4 received placebo. Single center study (France): 6 subjects received 0. 01 mg/kg, 11 received 0. 02 mg/kg and 6 received placebo. V体育安卓版.

Results: Resiquimod 0. 01 mg/kg was tolerated; two 0. 2 mg/kg subjects discontinued treatment. More subjects reported severe grade adverse events at 0. 02 mg/kg; events were consistent with systemic cytokine induction, including fever, headache, shivering, and lymphopenia. Mean maximum serum resiquimod concentrations were 3. 82+/-1. 47 and 7. 55+/-4. 17 ng/mL for 0. 01 mg/kg and 0. 02 mg/kg, respectively. At 0 V体育ios版. 02 mg/kg, two, three and one subjects had maximal reductions in viral levels of at least 1-, 2- and 3-logs, respectively; reductions were generally transient. Interferon-alpha levels appeared correlated with decreases in viral titer and lymphocyte counts, as well as increase in neutrophil counts. .

Conclusions: Oral administration of resiquimod 0. 02 mg/kg transiently reduced viral levels but was associated with adverse effects similar to interferon-alpha. VSports最新版本.