Systemic pharmacokinetics of intravitreal anti-VEGF medications in wet AMD treatment

Main Article Content

Marta Misiuk-Hojło
Karolina Czajor

Abstract

Modern therapy of wet forms of AMD is based on administration of medications in the form of intravitreal injections: bevacizumab, ranibizumab and aflibercept. The population of people exposed to a long-term effect of anti-VEGF preparations is continuously increasing. Due to the penetration of the preparations administered intravitreously into the blood circulation, the knowledge of the activity of the available preparations is particularly important in deciding about the commissioned treatment. They differ in molecular structure, binding affinity of VEGF and pharmacokinetics. Ranibizumab is characterized by a fast clearance from circulation and a short-term systemic exposure. A slower bevacizumab and aflibercept circulation clearance is related to the presence of the Fc fragment in the molecular structure. Further research on the effects of the reduction of VEGF concentration in serum is essential in the course of a long- -term anti-VEGF intravitreal preparation therapy, which may affect decisions about the administered medication and the dosing regimen.

Downloads

Download data is not yet available.

Article Details

How to Cite
1.
Misiuk-Hojło M, Czajor K. Systemic pharmacokinetics of intravitreal anti-VEGF medications in wet AMD treatment. Ophthatherapy [Internet]. 2016Mar.31 [cited 2024Mar.29];3(1):4-10. Available from: https://journalsmededu.pl/index.php/ophthatherapy/article/view/587
Section
Articles

References

1. Schmier JK, Levine JA. Economic impact of progression of age-related macular degeneration. US Ophthalmic Rev. 2013; 6(1): 52.
2. Wang JJ, Mitchell P, Smith W et al. Bilateral involvement by age related maculopathy lesions in a population. Br J Ophthalmol. 1998; 82(7): 743-7.
3. Klein R, Klein BE, Knudtson MD et al. Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology. 2007; 114(2): 253-62.
4. Ohm J. Über die Behandlung der Netzhautablösung durch operative entleerung der subretinalen flüssigkeit und einspritzen vom luft in den glaskörper. Albrecht von Graefes Arch Ophthalmol. 1911; (79): 442-50.
5. Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration. Nat Rev Immunol. 2013; 13(6): 438-51.
6. Stankiewicz A. Patogeneza zwyrodnienia plamki związanego z wiekiem. Zwyrodnienie plamki związane z wiekiem – przewodnik diagnostyki i terapii. Termedia, Poznań 2010: 9-16.
7. Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001; 280(6): C1358-66.
8. Fung AE, Rosenfeld PJ, Reichel E. The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol. 2006; 90(11): 1344-9.
9. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2005; 36(4): 331-5.
10. Rosenfeld PJ, Fung AE, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging. 2005; 36(4): 336-9.
11. Sun C, Klein R, Wong TY. Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study. Ophthalmology. 2009; 116(10): 1913-9.
12. Ikram MK, Mitchell P, Klein R et al. Age-related macular degeneration and long-term risk of stroke subtypes. Stroke J Cereb Circ. 2012; 43(6): 1681-3.
13. Hu CC, Ho JD, Lin HC. Neovascular age-related macular degeneration and the risk of stroke: a 5-year population-based follow-up study. Stroke J Cereb Circ. 2010; 41(4): 613-7.
14. Laude A, Tan LE, Wilson CG et al. Intravitreal therapy for neovascular age-related macular degeneration and inter-individual variations in vitreous pharmacokinetics. Prog Retin Eye Res. 2010; 29(6): 466-75.
15. Christoforidis JB, Carlton MM, Wang J et al. Anatomic and pharmacokinetic properties of intravitreal bevacizumab and ranibizumab after vitrectomy and lensectomy. Retina. 2013; 33(5): 946-52.
16. Kodjikian L, Souied EH, Mimoun G et al. Ranibizumab versus bevacizumab for neovascular age-related macular degeneration: results from the GEFAL Noninferiority Randomized Trial. Ophthalmology. 2013; 120(11): 2300-9.
17. Ternant D, Paintaud G. Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins. Expert Opin Biol Ther. 2005; 5(suppl 1): S37-7.
18. Zhang Y, Yao Z, Kaila N et al. Pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion or diabetic macular edema. Ophthalmology. 2014; 121(11): 2237-46.
19. Papadopoulos N, Martin J, Ruan Q et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012; 15(2): 171-85.
20. Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol. 2009; 6(8): 465-77.
21. Krohne TU, Eter N, Holz FG et al. Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection in humans. Am J Ophthalmol. 2008; 146(4): 508-12.
22. Zhu Q, Ziemssen F, Henke-Fahle S et al. Vitreous levels of bevacizumab and vascular endothelial growth factor-A in patients with choroidal neovascularization. Ophthalmology. 2008; 115(10): 1750-5.
23. Nomoto H, Shiraga F, Kuno N et al. Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits. Invest Ophthalmol Vis Sci. 2009; 50(10): 4807-13.
24. Bakri SJ, Snyder MR, Reid JM et al. Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology. 2007; 114(5): 855-9.
25. Stewart MW. What are the half-lives of ranibizumab and aflibercept (VEGF Trap-eye) in human eyes? Calculations with a mathematical model. Eye Rep. 2011; 1(1): 5.
26. Krohne TU, Liu Z, Holz FG et al. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. Am J Ophthalmol. 2012; 154(4): 682-6.e2.
27. Bakri SJ, Snyder MR, Reid JM et al. Pharmacokinetics of intravitreal ranibizumab (Lucentis). Ophthalmology. 2007; 114(12): 2179-82.
28. Park SJ, Oh J, Kim YK et al. Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model. Eye. 2015; 29(4): 561-8.
29. Zehetner C, Kirchmair R, Huber S et al. Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema. Br J Ophthalmol. 2013; 97(4): 454-59.
30. Wang X, Sawada T, Sawada O et al. Serum and plasma vascular endothelial growth factor concentrations before and after intravitreal injection of aflibercept or ranibizumab for age related macular degeneration. Am J Ophthalmol. 2014; 158(4): 738-44.e1.
31. Avery RL, Castellarin AA, Steinle NC et al. Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD. Br J Ophthalmol. 2014; 98(12): 1636-41.
32. Heier JS, Brown DM, Chong V et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012; 119(12): 2537-48.
33. Rouvas A, Liarakos VS, Theodossiadis P et al. The effect of intravitreal ranibizumab on the fellow untreated eye with subfoveal scarring due to exudative age-related macular degeneration. Ophthalmologica. 2009; 223(6): 383-9.
34. Miura M, Iwasaki T, Goto H. Intravitreal aflibercept for polypoidal choroidal vasculopathy after developing ranibizumab tachyphylaxis. Clin Ophthalmol. 2013; 7: 1591-5.
35. Chakravarthy U, Harding SP, Rogers CA et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet Lond Engl. 2013; 382(9900): 1258-67.