Comparison of human ocular distribution of bimatoprost and latanoprost

Parul Ichhpujani, L. Jay Katz, G. Holló, Carol L. Shields, Jerry A. Shields, Brian Marr, Ralph Eagle, Heryberto Alvim, Sheryl S. Wizov, Andrew Acheampong, June Chen, Larry A. Wheeler

Research output: Article

13 Citations (Scopus)

Abstract

Purpose: This study investigated the ocular distribution of bimatoprost, latanoprost, and their acid hydrolysis products in the aqueous humor, cornea, sclera, iris, and ciliary body of patients treated with a single topical dose of 0.03% bimatoprost or 0.005% latanoprost for understanding concentration- activity relationships. Methods: Thirty-one patients undergoing enucleation for an intraocular tumor not affecting the anterior part of the globe were randomized to treatment with bimatoprost or latanoprost at 1, 3, 6 or 12 h prior to surgery. Concentrations of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid in the human aqueous and ocular tissues were measured using liquid chromatography tandem mass spectrometry. Results: Following topical administration, intact bimatoprost was distributed in human eyes with a rank order of cornea/sclera >iris/ciliary body >aqueous humor. Bimatoprost acid was also detected in these tissues, where its low levels in the cornea relative to that of latanoprost acid indicated that bimatoprost hydrolysis was limited. Latanoprost behaved as a prodrug that entered eyes predominantly via the corneal route. Levels of latanoprost acid were distributed as cornea >>aqueous humor>iris>sclera>ciliary body. Conclusions: Our study provided experimental evidence that levels of bimatoprost in relevant ocular tissues, and not only aqueous humor, are needed to understand the mechanisms by which bimatoprost lowers intraocular pressure (IOP) in human subjects. The data suggest that bimatoprost reached the target tissues favoring the conjunctival/scleral absorption route. Findings of intact bimatoprost in the target ciliary body indicated its direct involvement in reducing IOP. However, bimatoprost acid may have only a limited contribution on the basis that bimatoprost has greater/similar IOP-lowering efficacy than latanoprost, yet bimatoprost acid levels were a fraction of latanoprost acid levels in the aqueous humor and cornea and only sporadically detectable in the ciliary body. In this report, human ocular tissues were examined concurrently with aqueous humor for the in vivo distribution of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid.

Original languageEnglish
Pages (from-to)134-145
Number of pages12
JournalJournal of Ocular Pharmacology and Therapeutics
Volume28
Issue number2
DOIs
Publication statusPublished - ápr. 1 2012

Fingerprint

latanoprost
Aqueous Humor
Acids
Ciliary Body
Cornea
Sclera
Iris
Intraocular Pressure
Bimatoprost

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Ophthalmology
  • Pharmacology

Cite this

Ichhpujani, P., Katz, L. J., Holló, G., Shields, C. L., Shields, J. A., Marr, B., ... Wheeler, L. A. (2012). Comparison of human ocular distribution of bimatoprost and latanoprost. Journal of Ocular Pharmacology and Therapeutics, 28(2), 134-145. https://doi.org/10.1089/jop.2011.0097

Comparison of human ocular distribution of bimatoprost and latanoprost. / Ichhpujani, Parul; Katz, L. Jay; Holló, G.; Shields, Carol L.; Shields, Jerry A.; Marr, Brian; Eagle, Ralph; Alvim, Heryberto; Wizov, Sheryl S.; Acheampong, Andrew; Chen, June; Wheeler, Larry A.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 28, No. 2, 01.04.2012, p. 134-145.

Research output: Article

Ichhpujani, P, Katz, LJ, Holló, G, Shields, CL, Shields, JA, Marr, B, Eagle, R, Alvim, H, Wizov, SS, Acheampong, A, Chen, J & Wheeler, LA 2012, 'Comparison of human ocular distribution of bimatoprost and latanoprost', Journal of Ocular Pharmacology and Therapeutics, vol. 28, no. 2, pp. 134-145. https://doi.org/10.1089/jop.2011.0097
Ichhpujani, Parul ; Katz, L. Jay ; Holló, G. ; Shields, Carol L. ; Shields, Jerry A. ; Marr, Brian ; Eagle, Ralph ; Alvim, Heryberto ; Wizov, Sheryl S. ; Acheampong, Andrew ; Chen, June ; Wheeler, Larry A. / Comparison of human ocular distribution of bimatoprost and latanoprost. In: Journal of Ocular Pharmacology and Therapeutics. 2012 ; Vol. 28, No. 2. pp. 134-145.
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AU - Shields, Jerry A.

AU - Marr, Brian

AU - Eagle, Ralph

AU - Alvim, Heryberto

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AU - Chen, June

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N2 - Purpose: This study investigated the ocular distribution of bimatoprost, latanoprost, and their acid hydrolysis products in the aqueous humor, cornea, sclera, iris, and ciliary body of patients treated with a single topical dose of 0.03% bimatoprost or 0.005% latanoprost for understanding concentration- activity relationships. Methods: Thirty-one patients undergoing enucleation for an intraocular tumor not affecting the anterior part of the globe were randomized to treatment with bimatoprost or latanoprost at 1, 3, 6 or 12 h prior to surgery. Concentrations of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid in the human aqueous and ocular tissues were measured using liquid chromatography tandem mass spectrometry. Results: Following topical administration, intact bimatoprost was distributed in human eyes with a rank order of cornea/sclera >iris/ciliary body >aqueous humor. Bimatoprost acid was also detected in these tissues, where its low levels in the cornea relative to that of latanoprost acid indicated that bimatoprost hydrolysis was limited. Latanoprost behaved as a prodrug that entered eyes predominantly via the corneal route. Levels of latanoprost acid were distributed as cornea >>aqueous humor>iris>sclera>ciliary body. Conclusions: Our study provided experimental evidence that levels of bimatoprost in relevant ocular tissues, and not only aqueous humor, are needed to understand the mechanisms by which bimatoprost lowers intraocular pressure (IOP) in human subjects. The data suggest that bimatoprost reached the target tissues favoring the conjunctival/scleral absorption route. Findings of intact bimatoprost in the target ciliary body indicated its direct involvement in reducing IOP. However, bimatoprost acid may have only a limited contribution on the basis that bimatoprost has greater/similar IOP-lowering efficacy than latanoprost, yet bimatoprost acid levels were a fraction of latanoprost acid levels in the aqueous humor and cornea and only sporadically detectable in the ciliary body. In this report, human ocular tissues were examined concurrently with aqueous humor for the in vivo distribution of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid.

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