Safety and pharmacokinetics of the antiorthopoxvirus compound ST-246 following repeat oral dosing in healthy adult subjects
Autor: | Jean M. Clarke, Michael L. Corrado, Tove' C. Bolken, Margaret Pickens, Kevin F. Jones, Shanthakumar R. Tyavanagimatt, Thomas Marbury, Jarasvech Chinsangaram, Deborah Tien, Robert Jordan, Annie Frimm, Patrick Landis, Dennis E. Hruby |
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Rok vydání: | 2010 |
Předmět: |
Adult
Male Adolescent Administration Oral Urine Orthopoxvirus Poxviridae Infections Pharmacology Isoindoles Antiviral Agents law.invention Young Adult Pharmacokinetics Randomized controlled trial Double-Blind Method law Medicine Humans Pharmacology (medical) Dosing Adverse effect business.industry Half-life Middle Aged Infectious Diseases Tolerability Pharmacodynamics Benzamides Female business Half-Life |
Zdroj: | Antimicrobial agents and chemotherapy. 54(6) |
ISSN: | 1098-6596 |
Popis: | ST-246, a novel compound that inhibits egress of orthopoxvirus from infected cells, is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, placebo-controlled, escalating multiple-dose study was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 administered as a single daily oral dose of 250, 400, or 800 mg for 21 days to nonfasting healthy human volunteers. ST-246 appeared to be well tolerated, with no serious adverse events (AEs). Headache, for which one subject in the 800-mg group discontinued the study, was the most commonly reported AE in all treatment groups. The multiple-dose pharmacokinetics of ST-246 was well characterized. The day 21 mean elimination half-lives were calculated at 18.8, 19.8, and 20.7 h for each of the 250-, 400-, and 800-mg/day dose groups, respectively. Steady state was reached by day 6 (within 3 to 5 half-lives), saturable absorption was observed at the 800-mg dose level, and the fraction of parent drug excreted in the urine was very low. Based on these results, administration of 400 mg/day ST-246 can be expected to provide plasma concentrations above the efficacious concentration demonstrated in nonhuman primate models in earlier studies. |
Databáze: | OpenAIRE |
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