Abstract | OBJECTIVE: METHODS: RESULTS: Twice-daily gavage of pazopanib, 100 mg/kg, suppressed the development of CNV by 93%. Treatment of established CNV between days 7 and 14 with 8, 40, or 200 mg/kg per day reduced CNV by 0%, 58%, and 71%, respectively. Substantial regression (40%) of CNV was also achieved after periocular injection of pazopanib. A single oral dose of 4 or 100 mg/kg resulted in an area under the curve from time 0 to the last quantifiable concentration of 129.6 and 752.0 microg x h/mL, respectively. After 7 days of 4, 20, or 100 mg/kg twice a day by gavage, plasma levels were 1300, 4900, and 5800 ng/mL and levels in the retina/choroid were 4800, 28 800, and 38 000 ng/g of tissue. CONCLUSIONS: Orally administered pazopanib has good bioavailability to the retina/choroid and strongly suppresses CNV in mice. Treatment with pazopanib after CNV is established causes dose-dependent regression of CNV. CLINICAL RELEVANCE:
Pazopanib may be useful for treatment of CNV in humans.
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Authors | Kyoichi Takahashi, Yoshitsugu Saishin, Yumiko Saishin, Andrew G King, Robert Levin, Peter A Campochiaro |
Journal | Archives of ophthalmology (Chicago, Ill. : 1960)
(Arch Ophthalmol)
Vol. 127
Issue 4
Pg. 494-9
(Apr 2009)
ISSN: 1538-3601 [Electronic] United States |
PMID | 19365030
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Indazoles
- Protein Kinase Inhibitors
- Pyrimidines
- Sulfonamides
- pazopanib
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Topics |
- Administration, Oral
- Angiogenesis Inhibitors
(pharmacokinetics, therapeutic use)
- Animals
- Biological Availability
- Choroid
(metabolism)
- Choroidal Neovascularization
(physiopathology, prevention & control)
- Chromatography, High Pressure Liquid
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Female
- Indazoles
- Mice
- Mice, Inbred C57BL
- Protein Kinase Inhibitors
(pharmacokinetics, therapeutic use)
- Pyrimidines
(pharmacokinetics, therapeutic use)
- Retina
(metabolism)
- Sulfonamides
(pharmacokinetics, therapeutic use)
- Tissue Distribution
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