Pharmacokinetic Study of Intravitreal Aflibercept in Humans With Neovascular Age-Related Macular Degeneration

Diana, V.; Rhoades, William; Nguyen, Quan Dong

doi:10.1097/iae.0000000000002566

Cited by 49 publications

(38 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Molecular weight and parameter values used as a basis for simulations are summarized from published literature (Table 1). [2][3][4][5]7,8,[12][13][14][15][16][17][18][19][20][21][22] Initial vitreous molar drug concentrations were based on a vitreous volume of 4 mL and clinical doses of 2 mg for IVT-AFL, 6 mg for IVT-BRO, and 0.5 mg for IVT-RAN. Flip-flop PK relationships for each agent were assumed, consistent with Hutton-Smith et al 23 and Caruso et al, 24 with aqueous ≈ vitreous half-life for IVT-AFL and IVT-RAN, and serum ≈ vitreous half-life for IVT-BRO.…”

Section: Model Developmentmentioning

confidence: 99%

“…Selected aflibercept half-life for model: 9.1 days Rationale for selection: Do et al 13 is the only publication that reports the aqueous half-life of aflibercept in nAMD patients. The mean was used (a conservative estimate, but consistent with using the mean for other anti-VEGF) and the median of 11 days was examined in sensitivity analyses.…”

Section: Single-dose Pk Simulations After Intravitreal Dosingmentioning

confidence: 99%

See 1 more Smart Citation

Durability of VEGF Suppression With Intravitreal Aflibercept and Brolucizumab: Using Pharmacokinetic Modeling to Understand Clinical Outcomes

Eißing

Stewart

Qian

et al. 2021

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

To investigate whether vascular endothelial growth factor (VEGF)suppression durations contribute to our understanding of clinical trial outcomes by simulating vitreous molar concentrations (C vm ) of intravitreal aflibercept (IVT-AFL) and brolucizumab (IVT-BRO) using pharmacokinetic (PK) modeling.Methods: A PK model simulated C vm after single-dose IVT-AFL, IVT-BRO, and ranibizumab (IVT-RAN), and extrapolated intraocular VEGF-suppression thresholds and durations. Vitreous PK after multidose regimens used in studies of IVT-AFL versus IVT-BRO were simulated and compared with best-corrected visual acuity (BCVA) data.Results: C vm peaked higher (C max ) and decreased more quickly to the VEGF-suppression threshold and minimum (C min ) levels with IVT-BRO than with IVT-AFL, consistent with their molar doses calculated using molecular weights and vitreous half-lives (26 kDa and 115 kDa; 4.4-5.1 and 9.1-11 days, respectively). The mean VEGF suppression durations were 71 days for IVT-AFL 2 mg and 51 (48-59) days for IVT-BRO 6 mg. Based on dosing in OSPREY (matched dosing to week [w]32 for both agents; thereafter, IVT-AFL every eight weeks [q8w] and IVT-BRO q12w for the last two doses [w32→w44 and w44→w56]), IVT-BRO showed wider C max -C min fluctuations than IVT-AFL. The IVT-BRO C min fell below the VEGF-suppression threshold at timepoints near w56, when decreases in BCVA were also observed. The IVT-AFL vitreous C min remained above the suppression threshold through w56, where BCVA gains were maintained. Conclusions:The PK-modeled mean VEGF-suppression duration for IVT-BRO was substantially shorter than that published for IVT-AFL and may not be sufficient to effectively suppress VEGF throughout q12w dosing.Translational Relevance: The PK modeling suggests that more patients may be maintained on ≥q12w dosing with IVT-AFL than with IVT-BRO.

show abstract

Section: Model Developmentmentioning

confidence: 99%

Section: Single-dose Pk Simulations After Intravitreal Dosingmentioning

confidence: 99%

Durability of VEGF Suppression With Intravitreal Aflibercept and Brolucizumab: Using Pharmacokinetic Modeling to Understand Clinical Outcomes

Eißing

Stewart

Qian

et al. 2021

Trans. Vis. Sci. Tech.

View full text Add to dashboard Cite

show abstract

“…A study conducted in five patients with AMD found an aqueous half-life of approximately nine days based on aqueous samples. They also found very low plasma levels, suggesting a lack of substantial plasma exposure [59].…”

Section: Pharmacokinetics Of Anti-vefg Drugsmentioning

confidence: 99%

Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration

et al. 2019

View full text Add to dashboard Cite

Intravitreal administration of anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for Age-Related Macular Degeneration; however, the knowledge of their pharmacokinetics is limited. A comprehensive review of the preclinical and clinical pharmacokinetic data that were obtained in different studies with intravitreal bevacizumab, ranibizumab, and aflibercept has been conducted. Moreover, the factors that can influence the vitreous pharmacokinetics of these drugs, as well as the methods that were used in the studies for analytical determination, have been exposed. These anti-VEGF drugs present different charge and molecular weights, which play an important role in vitreous distribution and elimination. The pharmacokinetic parameters that were collected differ depending on the species that were involved in the studies and on physiological and pathological conditions, such as vitrectomy and lensectomy. Knowledge of the intravitreal pharmacokinetics of the anti-VEGF drugs that were used in clinical practice is of vital importance.

show abstract

“…Until now, there are no available data on the half-life of aflibercept in the human eye. e most recent study of Do et al has shown that the half-life of aflibercept in the aqueous humor after a single intravitreal injection in five patients with neovascular AMD was 11 days [16].…”

Section: Discussionmentioning

confidence: 99%

Effect of Repeated Intravitreal Ranibizumab and Aflibercept Injections on the Cornea in Patients with Age-Related Macular Degeneration

Urban

Szwabowicz²,

Bakunowicz-Łazarczyk

2020

Journal of Ophthalmology

View full text Add to dashboard Cite

Purpose. To assess the effect of repeated intravitreal ranibizumab injections (RI) and aflibercept injections (AI) on the corneal endothelium and central corneal thickness (CCT) in patients with age-related macular degeneration (AMD). Materials and Methods. In the retrospective study, 110 eyes of 106 patients, aged 52 to 93 years, were analyzed. Fifty eyes were treated only with RI (I group), and 60 eyes were treated only with AI (II group). Every patient received one intravitreal injection of 0.5 mg of ranibizumab once a month or 2 mg of aflibercept for 3 subsequent months. Each patient received only 3 injections during the whole observation period. Corneal analysis was obtained with the specular microscope. Examinations were performed before initial treatment, after each injection, and 6 months after the first injection. Analysis included corneal endothelial cell density (ECD), hexagonal cell percentage (% Hex), coefficient of variation (CoV), and CCT. Results. There was a statistically significant ECD loss, regardless of the type of the anti-VEGF agent. The mean ECD value in the I group was 2397 ± 459 cells/mm2 before RI, 2389 ± 459 cells/mm2 after the first RI, 2386 ± 467 cells/mm2 after the second RI, 2378 ± 475 cells/mm2 after the third RI, and 2357 ± 460 cells/mm2 6 months after the first RI. The mean ECD value in the II group was 2448 ± 493 cells/mm2 before treatment, 2456 ± 498 cells/mm2 after the first AI, 2426 ± 496 cells/mm2 after the second AI, 2402 ± 488 cells/mm2 after the third AI, and 2348 ± 473 cells/mm2 6 months after the first AI. In comparison with the group treated with RI, the group treated with AI presented a greater ECD loss at each measuring point. The percentage of hexagonal cells was decreased in both groups. There was a slight increase in polymegathism in both treated groups. Ranibizumab proved to cause a small increase in CCT, while CCT remained unchanged in the aflibercept group. Conclusions. Repeated intravitreal injections of 0.5 mg of ranibizumab or 2 mg of aflibercept can influence the morphology of the corneal endothelium but not CCT.

show abstract

Pharmacokinetic Study of Intravitreal Aflibercept in Humans With Neovascular Age-Related Macular Degeneration

Cited by 49 publications

References 12 publications

Durability of VEGF Suppression With Intravitreal Aflibercept and Brolucizumab: Using Pharmacokinetic Modeling to Understand Clinical Outcomes

Durability of VEGF Suppression With Intravitreal Aflibercept and Brolucizumab: Using Pharmacokinetic Modeling to Understand Clinical Outcomes

Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration

Effect of Repeated Intravitreal Ranibizumab and Aflibercept Injections on the Cornea in Patients with Age-Related Macular Degeneration

Contact Info

Product

Resources

About