Pharmacokinetics of systemic versus focal carboplatin chemotherapy in the rabbit eye: Possible implication in the treatment of retinoblastoma

Brandy C. Hayden, Maria Elena Jockovich, Timothy G. Murray, Monika Voigt, Peter Milne, Martina Kralinger, William J Feuer, Eleut Hernandez, Jean-Marie A Parel

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To characterize the pharmacology and toxicity of intravenous versus focal carboplatin delivery in the rabbit eye. METHODS. Pharmacological distribution of carboplatin was examined in New Zealand White Rabbits after a single intravenous infusion of carboplatin (18.7 mg/kg of body weight), a single subconjunctival carboplatin injection (5.0 mg/400 μL), or a single application of carboplatin delivered by Coulomb-controlled iontophoresis (CCI; 14 mg/mL carboplatin, 5.0 mA/cm2, 20 minutes). After each treatment, animals were euthanatized, and the eyes analyzed at 1, 2, 6, or 24 hours by atomic absorption spectroscopy to determine carboplatin concentration in ocular structures. Potential toxicity of focally delivered carboplatin was assessed by histology after six cycles of 5.0 mg carboplatin delivered by subconjunctival injection or six transscleral carboplatin CCI applications at 72-hour intervals (14.0 mg/mL, 20 minutes at 2.5 mA). RESULTS. Determination of concentrations through atomic absorption spectroscopy in the retina, choroid, vitreous humor, and optic nerve after subconjunctival injection or iontophoretic carboplatin delivery revealed significantly higher levels than those achieved with intravenous administration. Carboplatin concentrations in the blood plasma were found to be significantly higher after intravenous delivery than after focal delivery by subconjunctival injection or CCI. No evidence of ocular toxicity was detected after focally delivered Carboplatin. CONCLUSIONS. Focal administration of carboplatin using subconjunctival or noninvasive CCI safely and effectively transmits this chemotherapeutic drug into the target tissues of the retina, choroid, vitreous, and optic nerve. These results suggest that focal carboplatin delivery may effectively increase intraorbital carboplatin concentrations while decreasing systemic exposure to this cytotoxic drug.

Original languageEnglish
Pages (from-to)3644-3649
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume45
Issue number10
DOIs
StatePublished - Oct 1 2004

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Retinoblastoma
Carboplatin
Pharmacokinetics
Rabbits
Drug Therapy
Therapeutics
Injections
Choroid
Optic Nerve
Retina
Spectrum Analysis
Pharmacology
Vitreous Body
Iontophoresis
Intravenous Infusions
Pharmaceutical Preparations
Intravenous Administration

ASJC Scopus subject areas

  • Ophthalmology

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Pharmacokinetics of systemic versus focal carboplatin chemotherapy in the rabbit eye : Possible implication in the treatment of retinoblastoma. / Hayden, Brandy C.; Jockovich, Maria Elena; Murray, Timothy G.; Voigt, Monika; Milne, Peter; Kralinger, Martina; Feuer, William J; Hernandez, Eleut; Parel, Jean-Marie A.

In: Investigative Ophthalmology and Visual Science, Vol. 45, No. 10, 01.10.2004, p. 3644-3649.

Research output: Contribution to journalArticle

Hayden, Brandy C. ; Jockovich, Maria Elena ; Murray, Timothy G. ; Voigt, Monika ; Milne, Peter ; Kralinger, Martina ; Feuer, William J ; Hernandez, Eleut ; Parel, Jean-Marie A. / Pharmacokinetics of systemic versus focal carboplatin chemotherapy in the rabbit eye : Possible implication in the treatment of retinoblastoma. In: Investigative Ophthalmology and Visual Science. 2004 ; Vol. 45, No. 10. pp. 3644-3649.
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abstract = "PURPOSE. To characterize the pharmacology and toxicity of intravenous versus focal carboplatin delivery in the rabbit eye. METHODS. Pharmacological distribution of carboplatin was examined in New Zealand White Rabbits after a single intravenous infusion of carboplatin (18.7 mg/kg of body weight), a single subconjunctival carboplatin injection (5.0 mg/400 μL), or a single application of carboplatin delivered by Coulomb-controlled iontophoresis (CCI; 14 mg/mL carboplatin, 5.0 mA/cm2, 20 minutes). After each treatment, animals were euthanatized, and the eyes analyzed at 1, 2, 6, or 24 hours by atomic absorption spectroscopy to determine carboplatin concentration in ocular structures. Potential toxicity of focally delivered carboplatin was assessed by histology after six cycles of 5.0 mg carboplatin delivered by subconjunctival injection or six transscleral carboplatin CCI applications at 72-hour intervals (14.0 mg/mL, 20 minutes at 2.5 mA). RESULTS. Determination of concentrations through atomic absorption spectroscopy in the retina, choroid, vitreous humor, and optic nerve after subconjunctival injection or iontophoretic carboplatin delivery revealed significantly higher levels than those achieved with intravenous administration. Carboplatin concentrations in the blood plasma were found to be significantly higher after intravenous delivery than after focal delivery by subconjunctival injection or CCI. No evidence of ocular toxicity was detected after focally delivered Carboplatin. CONCLUSIONS. Focal administration of carboplatin using subconjunctival or noninvasive CCI safely and effectively transmits this chemotherapeutic drug into the target tissues of the retina, choroid, vitreous, and optic nerve. These results suggest that focal carboplatin delivery may effectively increase intraorbital carboplatin concentrations while decreasing systemic exposure to this cytotoxic drug.",
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T1 - Pharmacokinetics of systemic versus focal carboplatin chemotherapy in the rabbit eye

T2 - Possible implication in the treatment of retinoblastoma

AU - Hayden, Brandy C.

AU - Jockovich, Maria Elena

AU - Murray, Timothy G.

AU - Voigt, Monika

AU - Milne, Peter

AU - Kralinger, Martina

AU - Feuer, William J

AU - Hernandez, Eleut

AU - Parel, Jean-Marie A

PY - 2004/10/1

Y1 - 2004/10/1

N2 - PURPOSE. To characterize the pharmacology and toxicity of intravenous versus focal carboplatin delivery in the rabbit eye. METHODS. Pharmacological distribution of carboplatin was examined in New Zealand White Rabbits after a single intravenous infusion of carboplatin (18.7 mg/kg of body weight), a single subconjunctival carboplatin injection (5.0 mg/400 μL), or a single application of carboplatin delivered by Coulomb-controlled iontophoresis (CCI; 14 mg/mL carboplatin, 5.0 mA/cm2, 20 minutes). After each treatment, animals were euthanatized, and the eyes analyzed at 1, 2, 6, or 24 hours by atomic absorption spectroscopy to determine carboplatin concentration in ocular structures. Potential toxicity of focally delivered carboplatin was assessed by histology after six cycles of 5.0 mg carboplatin delivered by subconjunctival injection or six transscleral carboplatin CCI applications at 72-hour intervals (14.0 mg/mL, 20 minutes at 2.5 mA). RESULTS. Determination of concentrations through atomic absorption spectroscopy in the retina, choroid, vitreous humor, and optic nerve after subconjunctival injection or iontophoretic carboplatin delivery revealed significantly higher levels than those achieved with intravenous administration. Carboplatin concentrations in the blood plasma were found to be significantly higher after intravenous delivery than after focal delivery by subconjunctival injection or CCI. No evidence of ocular toxicity was detected after focally delivered Carboplatin. CONCLUSIONS. Focal administration of carboplatin using subconjunctival or noninvasive CCI safely and effectively transmits this chemotherapeutic drug into the target tissues of the retina, choroid, vitreous, and optic nerve. These results suggest that focal carboplatin delivery may effectively increase intraorbital carboplatin concentrations while decreasing systemic exposure to this cytotoxic drug.

AB - PURPOSE. To characterize the pharmacology and toxicity of intravenous versus focal carboplatin delivery in the rabbit eye. METHODS. Pharmacological distribution of carboplatin was examined in New Zealand White Rabbits after a single intravenous infusion of carboplatin (18.7 mg/kg of body weight), a single subconjunctival carboplatin injection (5.0 mg/400 μL), or a single application of carboplatin delivered by Coulomb-controlled iontophoresis (CCI; 14 mg/mL carboplatin, 5.0 mA/cm2, 20 minutes). After each treatment, animals were euthanatized, and the eyes analyzed at 1, 2, 6, or 24 hours by atomic absorption spectroscopy to determine carboplatin concentration in ocular structures. Potential toxicity of focally delivered carboplatin was assessed by histology after six cycles of 5.0 mg carboplatin delivered by subconjunctival injection or six transscleral carboplatin CCI applications at 72-hour intervals (14.0 mg/mL, 20 minutes at 2.5 mA). RESULTS. Determination of concentrations through atomic absorption spectroscopy in the retina, choroid, vitreous humor, and optic nerve after subconjunctival injection or iontophoretic carboplatin delivery revealed significantly higher levels than those achieved with intravenous administration. Carboplatin concentrations in the blood plasma were found to be significantly higher after intravenous delivery than after focal delivery by subconjunctival injection or CCI. No evidence of ocular toxicity was detected after focally delivered Carboplatin. CONCLUSIONS. Focal administration of carboplatin using subconjunctival or noninvasive CCI safely and effectively transmits this chemotherapeutic drug into the target tissues of the retina, choroid, vitreous, and optic nerve. These results suggest that focal carboplatin delivery may effectively increase intraorbital carboplatin concentrations while decreasing systemic exposure to this cytotoxic drug.

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