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Pharmakokinetik intravitreal applizierter VEGF-Inhibitoren

Pharmacokinetics of intravitreally administered VEGF inhibitors

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Zusammenfassung

Hintergrund

Neben der topischen, periokulären und systemischen Gabe hat sich die intravitreale Injektion in den letzten Jahren als weiteres Standardverfahren der Medikamentenapplikation in der Augenheilkunde etabliert, insbesondere für die Therapie von Netzhauterkrankungen mit Substanzen zur Hemmung des gefäßendothelialen Wachstumsfaktors („vascular endothelial growth factor“, VEGF).

Material und Methoden

Es erfolgten eine selektive Literaturrecherche und eine Auswertung eigener Forschungsdaten.

Ergebnisse

Durch die intravitreale Gabe können hohe Wirkstoffspiegel im Zielgewebe bei gleichzeitig geringerer systemischer Exposition erreicht werden. In Abhängigkeit von Eigenschaften wie Molekulargewicht und Bindungsfähigkeit an den neonatalen Fc-Rezeptor können intravitreal applizierte VEGF-Inhibitoren nennenswerte Unterschiede in ihrer intraokulären und systemischen Pharmakokinetik aufweisen. Zusätzlich kann ihre Pharmakokinetik von Eigenschaften des individuellen Auges wie Bulbusvolumen, Glaskörperverflüssigung und vorangegangene Vitrektomie beeinflusst werden.

Schlussfolgerungen

Die Pharmakokinetik intravitreal applizierter Arzneistoffe bestimmt sowohl die Dauer des okulären Effekts als auch das Ausmaß der systemischen Exposition und besitzt somit klinische Relevanz im Hinblick auf Reinjektionsstrategie und systemische Sicherheit.

Abstract

Background

In addition to topical, periocular and systemic administration, intravitreal injection has been established in recent years as an additional standard procedure for ophthalmological drug delivery. This route of administration is now most frequently used for the therapy of retinal diseases with vascular endothelial growth factor (VEGF) inhibitors.

Material and methods

A selective literature review and an analysis of own research data were carried out.

Results

Intravitreal administration achieves high drug concentrations in the target tissue while minimizing systemic drug exposure. Depending on properties such as molecular weight and binding capacity to the neonatal Fc receptor, intravitreally applied VEGF inhibitors can exhibit relevant differences in intraocular and systemic pharmacokinetics. Moreover, the pharmacokinetics can be affected by properties of the individual eye, such as ocular volume, vitreous liquefaction, and prior vitrectomy.

Conclusions

Pharmacokinetics of intravitreally administered drugs determine both the duration of ocular effect and the degree of systemic exposure and are thus of clinical relevance with regard to the reinjection strategy and systemic safety.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. T.U. Krohne – Unterstützung von Forschungsprojekten und klinischen Studien: Alcon, Novartis; Beratung, Honorare, Reisekosten: Bayer, Heidelberg Engineering, Novartis. F.G. Holz – Unterstützung von Forschungsprojekten und klinischen Studien: Acucela, Alcon, Allergan, Bayer, Carl Zeiss Meditec, Genentech, Heidelberg Engineering, Novartis, Optos; Beratung, Honorare, Reisekosten: Acucela, Alcon, Allergan, Bayer, Genentech, Heidelberg Engineering, Novartis, Roche. C.H. Meyer – Unterstützung von Forschungsprojekten und klinischen Studien: Novartis, Allergan; Beratung, Honorare, Reisekosten: Bayer, GSK, Novartis. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Krohne, T., Holz, F. & Meyer, C. Pharmakokinetik intravitreal applizierter VEGF-Inhibitoren. Ophthalmologe 111, 113–120 (2014). https://doi.org/10.1007/s00347-013-2932-9

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  • DOI: https://doi.org/10.1007/s00347-013-2932-9

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