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 language | English |
|---|---|
| Pages (from-to) | 4807-4813 |
| Number of pages | 7 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 50 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2009 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
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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U2 - 10.1167/iovs.08-3148
DO - 10.1167/iovs.08-3148
M3 - Article
VL - 50
SP - 4807
EP - 4813
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 10
ER -