PMID- 20385870
OWN - NLM
STAT- MEDLINE
DCOM- 20100914
LR  - 20220808
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 54
IP  - 6
DP  - 2010 Jun
TI  - Safety and pharmacokinetics of the antiorthopoxvirus compound ST-246 following 
      repeat oral dosing in healthy adult subjects.
PG  - 2560-6
LID - 10.1128/AAC.01689-09 [doi]
AB  - 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.
FAU - Jordan, Robert
AU  - Jordan R
AD  - SIGA Technologies, Inc., Corvallis, OR 97333, USA.
FAU - Chinsangaram, Jarasvech
AU  - Chinsangaram J
FAU - Bolken, Tove' C
AU  - Bolken TC
FAU - Tyavanagimatt, Shanthakumar R
AU  - Tyavanagimatt SR
FAU - Tien, Deborah
AU  - Tien D
FAU - Jones, Kevin F
AU  - Jones KF
FAU - Frimm, Annie
AU  - Frimm A
FAU - Corrado, Michael L
AU  - Corrado ML
FAU - Pickens, Margaret
AU  - Pickens M
FAU - Landis, Patrick
AU  - Landis P
FAU - Clarke, Jean
AU  - Clarke J
FAU - Marbury, Thomas C
AU  - Marbury TC
FAU - Hruby, Dennis E
AU  - Hruby DE
LA  - eng
GR  - HHSN266200600014C/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100412
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzamides)
RN  - 0 (Isoindoles)
RN  - F925RR824R (tecovirimat)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Antiviral Agents/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Benzamides/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Double-Blind Method
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Isoindoles/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Orthopoxvirus/*drug effects
MH  - Poxviridae Infections/drug therapy
MH  - Young Adult
PMC - PMC2876426
EDAT- 2010/04/14 06:00
MHDA- 2010/09/15 06:00
PMCR- 2010/12/01
CRDT- 2010/04/14 06:00
PHST- 2010/04/14 06:00 [entrez]
PHST- 2010/04/14 06:00 [pubmed]
PHST- 2010/09/15 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - AAC.01689-09 [pii]
AID - 1689-09 [pii]
AID - 10.1128/AAC.01689-09 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2010 Jun;54(6):2560-6. doi: 10.1128/AAC.01689-09. 
      Epub 2010 Apr 12.