Anti-VEGFs clear bloodstream at different rates

Article

The systemic pharmacokinetics and pharmacodynamics of three anti-vascular endothelial growth factor (VEGF) treatments after they are administered intravitreally differ in ways that "may provide biological plausibility for potential differences in systemic safety risk," according to recently published research.

The systemic pharmacokinetics and pharmacodynamics of three anti-vascular endothelial growth factor (VEGF) treatments after they are administered intravitreally differ in ways that "may provide biological plausibility for potential differences in systemic safety risk," according to recently published research.

All three drugs enter the bloodstream quickly, Dr Robert L. Avery of California Retina Consultants, and colleagues found, but ranibizumab cleared the bloodstream very fast compared with bevacizumab and aflibercept. The findings of the study are relevant for patients such as those who have diabetic macular oedema, where questions have been raised about the dose size of treatment.

The investigators studied 56 people who had neovascular age-related macular degeneration that was treated with either intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg) or aflibercept (2.0 mg). They evaluated serum pharmacokinetics and plasma-free VEGF following the first and third injections.

After the first dose, the investigators found that:

  • Systemic exposure to aflibercept was 5-, 37- and 9-fold higher than that of ranibizumab.
  • Systemic exposure to bevacizumab was 9-, 310- and 35-fold higher than that of ranibizumab.

After the third dose, they found that:

  • Aflibercept and bevacizumab, but not ranibizumab, showed accumulation.
  • Aflibercept substantially suppressed plasma-free VEGF. Mean levels were below lower limit of quantitation (10 pg/mL) as soon as 3 hours after the dose until 7 or more days after the dose.
  • Mean free (unbound) VEGF levels with ranibizumab did not change much. The mean trough level was 14.4 pg/mL compared with the baseline of 17 pg/mL.

To read the study, go to the British Journal of Ophthalmology.

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