1.
Pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion or diabetic macular edema.
Zhang, Y, Yao, Z, Kaila, N, Kuebler, P, Visich, J, Maia, M, Tuomi, L, Ehrlich, JS, Rubio, RG, Campochiaro, PA
Ophthalmology. 2014;(11):2237-46
Abstract
OBJECTIVE To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME). DESIGN A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration. PARTICIPANTS Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly ranibizumab intravitreal administration. METHODS A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check. MAIN OUTCOME MEASURES Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients. RESULTS The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis. CONCLUSIONS The systemic pharmacokinetics of ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration. In all disease processes tested, ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure.
2.
Comparison of intravitreal triamcinolone acetonide with intravitreal bevacizumab for treatment of diabetic macular edema: a meta-analysis.
Zhang, Y, Ma, J, Meng, N, Li, H, Qu, Y
Current eye research. 2013;(5):578-87
Abstract
PURPOSE To compare the effects of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) injections for the treatment of diabetic macular edema (DME). METHODS A literature search was conducted using PUBMED, the Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Database. Pooled mean differences (MDs) for changes in visual acuity (VA) and central macular thickness (CMT) were calculated between groups receiving a single TA (4 mg) and bevacizumab (1.25 or 1.5 mg) from baseline to 4, 8, 12 and 24 weeks after treatment, respectively. Changes in intraocular pressure (IOP) were calculated between the two groups from baseline to 4, 8 and 12 weeks after treatment. RESULTS Eight trials (n = 434 eyes) comparing the efficacy of IVTA with IVB were included in the meta-analysis. Patients in the IVTA group demonstrated significant post-treatment improvement in VA compared with those in the IVB group at 4 (MD = -0.08; 95% confidence interval [CI]: -0.12 to -0.03; p = 0.0008), 8 (MD = -0.15; 95% CI: -0.20 to -0.11; p < 0.00001), 12 (MD = -0.11; 95% CI: -0.15 to -0.06; p < 0.0001) and 24 (MD = -0.05; 95% CI: -0.10 to -0.01; p = 0.02) weeks. After receiving IVTA, MDs in CMT decreased significantly at 4 weeks (MD = -40.05 μm; 95% CI: -75.29 to -4.81; p = 0.03). No significant differences in CMT were seen between the two groups at 8, 12 and 24 weeks post-treatment. Fluctuations of IOP were within normal range for both groups throughout the entire observation period. CONCLUSIONS Results of this meta-analysis suggest that IVTA is more effective for improving VA in DME. However, the CMT reduction with IVTA was unsustainable. Additional well-designed studies are needed to further investigate optimal interventions.