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

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.This was a comparative, interventional case series. Twenty-nine nonvitrectomized 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.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 μg/mL at baseline to 0.66 μg/mL at Day 57 and in Group B from 28.3 μg/mL at baseline to 0.00 μg/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 (R2 = 0.75) in Group A and 11.67 days (R2 = 0.91) in Group B. Similar half-times were calculated for globe size-corrected concentrations with 8.21 days (R2 = 0.81) in Group A and 11.17 days (R2 = 0.88) in Group B.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.