INTRAOCULAR PHARMACOKINETICS AFTER A SINGLE INTRAVITREAL INJECTION OF 1.5 MG VERSUS 3.0 MG OF BEVACIZUMAB IN HUMANS

Purpose: To compare the concentration of unbound bevacizumab in the anterior chamber of patients with macular edema, who received a single intravitreal injection of two different dosages. Methods: This was a comparative, interventional case series. Twenty-nine non-vitrectomized eyes of 29 patients with significant lens opacities and concurrent macular edema were included in the study. All patients were treated by a single dose of intravitreal injection of bevacizumab 1.5 mg (Group A, n = 13) or 3.0 mg (Group B, n = 16). Subsequent phacoemulsification and aspiration of an aqueous humor samples were performed at various intervals (1-60 days). The axial length of the globe was measured using the IOLMaster to calculate the total volume and corresponding globe size-corrected half-time. The concentration of unbound bevacizumab was measured by enzyme-linked immunosorbent assay and pharmacokinetic parameters including half-time of elimination. Results: The mean peak concentration was observed in both groups on the first day after intravitreal bevacizumab injection. The mean concentration of unbound bevacizumab ranged in Group A from 17.5 mu g/mL at baseline to 0.66 mu g/mL at Day 57 and in Group B from 28.3 mu g/mL at baseline to 0.00 mu g/mL at 54 days. The axial lengths of all injected eyes were not significantly different between Group A (mean values, 23.026 mm, SD 1.21) and Group B (mean, 23.313 mm, SD 1.00; P = 0.31). Regression analysis determined elimination half-time values of 7.85 days (R(2) = 0.75) in Group A and 11.67 days (R(2) = 0.91) in Group B. Similar half-times were calculated for globe size-corrected concentrations with 8.21 days (R(2) = 0.81) in Group A and 11.17 days (R(2) = 0.88) in Group B. Conclusion: Single-and double-dose injections have similar pharmacokinetic characteristics in a first-order exponential decay function. The globe size-corrected concentration and half-time did not affect the calculated half-time in both groups. Doubled dosing induced a higher peak concentration at baseline, but the presumed extended biologic active concentration was no longer statistically significant after 6 weeks. The application of twice the dosage does not double the duration of its efficacy; it rather appears to extend the pharmacological duration by 1 half-time or approximately 8 days to 11 days. RETINA 31: 1877-1884, 2011