Reversible Z-E isomerism and pharmaceutical implications for SU5416

Drug Dev Ind Pharm. 2005 Dec;31(10):1001-7. doi: 10.1080/03639040500306260.

Abstract

SU5416 (Z-isomer), the first in its class of angiogenesis inhibitors, in solution converts to the E-isomer following light exposure and reverts to the Z-isomer in the dark. Kinetics of this Z-E isomerism in pharmaceutical media is reported. Analytical solutions need light protection at 5 degrees C to maintain integrity. While E-isomer in light-exposed product increased to 0.9% in 24 hours, light-protected product showed no change (25 degrees C, 18 months). Infusate studies indicated that < 1.9% E-isomer will be dosed to patients and would likely convert to the Z-isomer, following administration. This report implies Z-E isomerism in SU5416 is controllable with no limitations towards ensuring pharmaceutical product quality.

MeSH terms

  • Algorithms
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / blood
  • Angiogenesis Inhibitors / chemistry*
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Excipients
  • Half-Life
  • Humans
  • In Vitro Techniques
  • Indoles / administration & dosage
  • Indoles / blood
  • Indoles / chemistry*
  • Isomerism
  • Kinetics
  • Plasma / chemistry
  • Pyrroles / administration & dosage
  • Pyrroles / blood
  • Pyrroles / chemistry*
  • Quality Control
  • Structure-Activity Relationship

Substances

  • Angiogenesis Inhibitors
  • Excipients
  • Indoles
  • Pyrroles
  • Semaxinib