Ocular aspirin distribution: A comparison of intravenous, topical, and coulomb-controlled iontophoresis administration

Monika Voigt, Martina Kralinger, Gerhard Kieselbach, Pascal Chapon, Scott Anagnoste, Brandy Hayden, Jean-Marie A Parel

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To evaluate the pharmacokinetics and safety of aspirin delivered by a single, noninvasive, transscleral, coulomb-controlled iontophoresis (CCI) treatment; topical application; or by one intravenous (IV) injection. METHODS. Forty-one adult New Zealand White rabbits received either a single IV injection, topical, or CCI administration of aspirin at a concentration of 10 mg/mL. Histologic evaluation was performed in four CCI-treated eyes to assess safety. Pharmacokinetic distribution in all ocular tissues and fluids was studied at 0.5, 1, 2, 4, 6, and 8 hours after the treatments. Immediately after death, the eyes were dissected and salicylic acid (SA) concentration was determined by HPLC analysis. Blood was sampled at 0.5, 1, 2, 4, 6, and 8 hours, and plasma SA levels for systemic distribution were measured by HPLC analysis. RESULTS. NO tissue damage was observed clinically or histologically. SA was found in all tissues and fluids throughout the study period of 8 hours. The highest concentrations of SA were observed with CCI immediately after treatment for all tissues and were the highest SA tissue peaks obtained by the studied delivery methods. IV administration demonstrated a delayed tissue peak of salicylate at 2 hours after administration. At 8 hours, ocular SA concentrations were in the same range for CCI and IV administration. IV injection resulted in blood plasma levels up to 28 times higher than CCI and remained significantly elevated until 8 hours after the treatments. CONCLUSIONS. CCI is a safe and effective method of administering aspirin to the eye while avoiding the systemic side effects associated with IV injection.

Original languageEnglish
Pages (from-to)3299-3306
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number10
StatePublished - Oct 1 2002

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Iontophoresis
Salicylic Acid
Aspirin
Intravenous Injections
Intravenous Administration
Pharmacokinetics
High Pressure Liquid Chromatography
Safety
Salicylates
Therapeutics
Rabbits

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Ocular aspirin distribution : A comparison of intravenous, topical, and coulomb-controlled iontophoresis administration. / Voigt, Monika; Kralinger, Martina; Kieselbach, Gerhard; Chapon, Pascal; Anagnoste, Scott; Hayden, Brandy; Parel, Jean-Marie A.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 10, 01.10.2002, p. 3299-3306.

Research output: Contribution to journalArticle

Voigt, Monika ; Kralinger, Martina ; Kieselbach, Gerhard ; Chapon, Pascal ; Anagnoste, Scott ; Hayden, Brandy ; Parel, Jean-Marie A. / Ocular aspirin distribution : A comparison of intravenous, topical, and coulomb-controlled iontophoresis administration. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 10. pp. 3299-3306.
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N2 - PURPOSE. To evaluate the pharmacokinetics and safety of aspirin delivered by a single, noninvasive, transscleral, coulomb-controlled iontophoresis (CCI) treatment; topical application; or by one intravenous (IV) injection. METHODS. Forty-one adult New Zealand White rabbits received either a single IV injection, topical, or CCI administration of aspirin at a concentration of 10 mg/mL. Histologic evaluation was performed in four CCI-treated eyes to assess safety. Pharmacokinetic distribution in all ocular tissues and fluids was studied at 0.5, 1, 2, 4, 6, and 8 hours after the treatments. Immediately after death, the eyes were dissected and salicylic acid (SA) concentration was determined by HPLC analysis. Blood was sampled at 0.5, 1, 2, 4, 6, and 8 hours, and plasma SA levels for systemic distribution were measured by HPLC analysis. RESULTS. NO tissue damage was observed clinically or histologically. SA was found in all tissues and fluids throughout the study period of 8 hours. The highest concentrations of SA were observed with CCI immediately after treatment for all tissues and were the highest SA tissue peaks obtained by the studied delivery methods. IV administration demonstrated a delayed tissue peak of salicylate at 2 hours after administration. At 8 hours, ocular SA concentrations were in the same range for CCI and IV administration. IV injection resulted in blood plasma levels up to 28 times higher than CCI and remained significantly elevated until 8 hours after the treatments. CONCLUSIONS. CCI is a safe and effective method of administering aspirin to the eye while avoiding the systemic side effects associated with IV injection.

AB - PURPOSE. To evaluate the pharmacokinetics and safety of aspirin delivered by a single, noninvasive, transscleral, coulomb-controlled iontophoresis (CCI) treatment; topical application; or by one intravenous (IV) injection. METHODS. Forty-one adult New Zealand White rabbits received either a single IV injection, topical, or CCI administration of aspirin at a concentration of 10 mg/mL. Histologic evaluation was performed in four CCI-treated eyes to assess safety. Pharmacokinetic distribution in all ocular tissues and fluids was studied at 0.5, 1, 2, 4, 6, and 8 hours after the treatments. Immediately after death, the eyes were dissected and salicylic acid (SA) concentration was determined by HPLC analysis. Blood was sampled at 0.5, 1, 2, 4, 6, and 8 hours, and plasma SA levels for systemic distribution were measured by HPLC analysis. RESULTS. NO tissue damage was observed clinically or histologically. SA was found in all tissues and fluids throughout the study period of 8 hours. The highest concentrations of SA were observed with CCI immediately after treatment for all tissues and were the highest SA tissue peaks obtained by the studied delivery methods. IV administration demonstrated a delayed tissue peak of salicylate at 2 hours after administration. At 8 hours, ocular SA concentrations were in the same range for CCI and IV administration. IV injection resulted in blood plasma levels up to 28 times higher than CCI and remained significantly elevated until 8 hours after the treatments. CONCLUSIONS. CCI is a safe and effective method of administering aspirin to the eye while avoiding the systemic side effects associated with IV injection.

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