Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits

Hiroyuki Nomoto, Fumio Shiraga, Noriyuki Kuno, Erika Kimura, Shinobu Fujii, Katsuhiko Shinomiya, Alex K. Nugent, Kazuyuki Hirooka, Tetsuya Baba

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops. METHODS. Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzymelinked immunosorbent assay at 1, 2, 4, and 12 weeks after administration. RESULTS. After intravitreal injection in the treated eye, the mean maximum concentrations (Cmax) of bevacizumab in the iris/ ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the Cmax was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the Cmax was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection. CONCLUSIONS. Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.

Original languageEnglish
Pages (from-to)4807-4813
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number10
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Pharmacokinetics
Intravitreal Injections
Rabbits
Ciliary Body
Choroid
Ophthalmic Solutions
Iris
Injections
Retina
Bevacizumab
Immunosorbents
Vascular Endothelial Growth Factor A
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits. / Nomoto, Hiroyuki; Shiraga, Fumio; Kuno, Noriyuki; Kimura, Erika; Fujii, Shinobu; Shinomiya, Katsuhiko; Nugent, Alex K.; Hirooka, Kazuyuki; Baba, Tetsuya.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 10, 2009, p. 4807-4813.

Research output: Contribution to journalArticle

Nomoto, Hiroyuki ; Shiraga, Fumio ; Kuno, Noriyuki ; Kimura, Erika ; Fujii, Shinobu ; Shinomiya, Katsuhiko ; Nugent, Alex K. ; Hirooka, Kazuyuki ; Baba, Tetsuya. / Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 10. pp. 4807-4813.
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abstract = "PURPOSE. To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops. METHODS. Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzymelinked immunosorbent assay at 1, 2, 4, and 12 weeks after administration. RESULTS. After intravitreal injection in the treated eye, the mean maximum concentrations (Cmax) of bevacizumab in the iris/ ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the Cmax was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the Cmax was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection. CONCLUSIONS. Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.",
author = "Hiroyuki Nomoto and Fumio Shiraga and Noriyuki Kuno and Erika Kimura and Shinobu Fujii and Katsuhiko Shinomiya and Nugent, {Alex K.} and Kazuyuki Hirooka and Tetsuya Baba",
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T1 - Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits

AU - Nomoto, Hiroyuki

AU - Shiraga, Fumio

AU - Kuno, Noriyuki

AU - Kimura, Erika

AU - Fujii, Shinobu

AU - Shinomiya, Katsuhiko

AU - Nugent, Alex K.

AU - Hirooka, Kazuyuki

AU - Baba, Tetsuya

PY - 2009

Y1 - 2009

N2 - PURPOSE. To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops. METHODS. Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzymelinked immunosorbent assay at 1, 2, 4, and 12 weeks after administration. RESULTS. After intravitreal injection in the treated eye, the mean maximum concentrations (Cmax) of bevacizumab in the iris/ ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the Cmax was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the Cmax was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection. CONCLUSIONS. Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.

AB - PURPOSE. To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops. METHODS. Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzymelinked immunosorbent assay at 1, 2, 4, and 12 weeks after administration. RESULTS. After intravitreal injection in the treated eye, the mean maximum concentrations (Cmax) of bevacizumab in the iris/ ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the Cmax was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the Cmax was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection. CONCLUSIONS. Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.

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