Pharmacokinetic comparison of a single oral dose of polymorph form i versus form V capsules of the antiorthopoxvirus compound ST-246 in human volunteers.

Abstract

ST-246, a novel compound that inhibits egress of orthopoxvirus from mammalian cells, is being tested as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, crossover, exploratory study was conducted to compare the pharmacokinetics (PK) of a single daily 400-mg oral dose of ST-246 polymorph form I versus polymorph form V administered to fed, healthy human volunteers. Both forms appeared to be well tolerated, with no serious adverse events. The order of administration of the two forms had no effect on the results of the PK analyses. Form I and form V both exhibited comparable plasma concentration versus time profiles, but complete bioequivalence between the two forms was not found. Maximum drug concentration (C(max)) met the bioequivalence criteria, as the 90% confidence interval (CI) was 80.6 to 96.9%. However, the area under the concentration-time curve from time zero to time t (AUC(0-t)) and AUC(0-∞) did not meet the bioequivalence criteria (CIs of 67.8 to 91.0% and 73.9 to 104.7%, respectively). The extent of absorption of form I, as defined by AUC(0-∞), was 11.7% lower than that of form V. Since ST-246 form I is more thermostable than form V, form I was selected for further development and use in all future studies.

• Authors: Jarasvech Chinsangaram, Kady M Honeychurch, Shanthakumar R Tyavanagimatt, Tove' C Bolken, Robert Jordan, Kevin F Jones, Thomas Marbury, Israel Lichtenstein, Margaret Pickens, Michael Corrado, Patrick Landis, Jean M Clarke, Annie M Frimm, Dennis E Hruby
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 56 Issue 7 Pg. 3582-6 (Jul 2012) ISSN: 1098-6596 [Electronic] United States
• PMID: 22526314 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• Benzamides
• Capsules
• Isoindoles
• tecovirimat

Topics

• Administration, Oral
• Adolescent
• Adult
• Antiviral Agents (administration & dosage, pharmacokinetics)
• Benzamides (administration & dosage, pharmacokinetics)
• Capsules (administration & dosage)
• Double-Blind Method
• Female
• Humans
• Isoindoles (administration & dosage, pharmacokinetics)
• Male
• Middle Aged
• Orthopoxvirus (drug effects)
• Young Adult