Reversible Z-E isomerism and pharmaceutical implications for SU5416.
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.
Sistla
Anand
A
Pfizer Inc., 10777 Science Center Drive, San Diego, CA 92121, USA. Sistla@Pfizer.com
Shenoy
Narmada
N
D000465:Algorithms; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005079:Excipients; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D007536:Isomerism; D007700:Kinetics; D010949:Plasma / Q000737:chemistry; D011758:Pyrroles / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*; D011786:Quality Control; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D005079:Excipients; D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib