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 language | English |
|---|---|
| Pages (from-to) | 134-145 |
| Number of pages | 12 |
| Journal | Journal of Ocular Pharmacology and Therapeutics |
| Volume | 28 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 1 2012 |
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ASJC Scopus subject areas
- Pharmacology (medical)
- Ophthalmology
- Pharmacology
Cite this
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: Contribution to journal › Article
}
TY - JOUR
T1 - Comparison of human ocular distribution of bimatoprost and latanoprost
AU - Ichhpujani, Parul
AU - Katz, L. Jay
AU - Holló, G.
AU - Shields, Carol L.
AU - Shields, Jerry A.
AU - Marr, Brian
AU - Eagle, Ralph
AU - Alvim, Heryberto
AU - Wizov, Sheryl S.
AU - Acheampong, Andrew
AU - Chen, June
AU - Wheeler, Larry A.
PY - 2012/4/1
Y1 - 2012/4/1
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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84859381344&partnerID=8YFLogxK
U2 - 10.1089/jop.2011.0097
DO - 10.1089/jop.2011.0097
M3 - Article
C2 - 22136089
AN - SCOPUS:84859381344
VL - 28
SP - 134
EP - 145
JO - Journal of Ocular Pharmacology and Therapeutics
JF - Journal of Ocular Pharmacology and Therapeutics
SN - 1080-7683
IS - 2
ER -