Anti-vascular endothelial growth factor activity in the bevacizumab and triamcinolone acetonide combination for intravitreal use.
OBJECTIVE
To find out if the combination for intravitreal use of the antibody bevacizumab (AvastinTM; Genentech, Inc., San Francisco, CA) and triamcinolone acetonide (TA) (Kenacort; Bristol-Myers Squibb, Anagni, Italy) could affect over time the anti -vascular endothelial growth factor (VEGF) activity of bevacizumab.


METHODS
Two different combined preparations were obtained, drawing up together 1.25 mg/0.05 mL of bevacizumab and 2 mg/0.05 mL (B+TA(2mg)) or 4 mg/0.05 mL (B+TA(4mg)) of TA into insulin syringes with 29-G needle. Control preparations were obtained with bevacizumab and an injectable solution (B). The syringes were stored refrigerated at 4 degrees C. The bevacizumab concentration was measured, through its binding to VEGF-165 isoform, at 48 hours and at 1 week.


RESULTS
No preparations showed statistically significant changes in bevacizumab concentration with time (p=0.74 for B+T(2mg), p=0.92 for B+T(4mg), p=0.57 for B). The B+TA(2mg) preparations showed a larger percentage of degradation of bevacizumab than the B+TA(4mg) preparations (28.4% versus 17.6% at 48 hours; 26.4% versus 18% at 1 week). The B control preparations showed the lowest drug degradation: 9.6% at 48 hours and 14.8% at 1 week.


CONCLUSIONS
After storage at 4 degrees C for 48 hours and 1 week, the combined preparations showed a larger reduction in bevacizumab concentration than the control preparations. No significant change was observed with the length of storage. The preparations obtained mixing 4 mg/0.05 mL of TA and 1.25 mg/0.05 mL of bevacizumab maintained the highest anti-VEGF activity over time.
Giammaria
Daniele
D
Department of Surgical Sciences, Eye Clinic, University of L'Aquila, L'Aquila - Italy. da.giamma@tin.it
Cinque
Benedetta
B
Di Lodovico
Domenico
D
Savastano
Maria Cristina
MC
Cifone
Maria Grazia
MG
Spadea
Leopoldo
L
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001682:Biological Availability; D004338:Drug Combinations; D004347:Drug Interactions; D004355:Drug Stability; D004356:Drug Storage; D005938:Glucocorticoids / Q000494:pharmacology*; D007267:Injections; D013594:Syringes; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D005938:Glucocorticoids; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D014222:Triamcinolone Acetonide