Levels of Bimatoprost Acid in the Aqueous Humour of Cataract Patients After Bimatoprost Treatment

Louis B. Cantor ^1*, Joni Hoop ¹, Darrell Wudunn ¹, Chi-Wah Yung ¹, Yara Catoira ¹, Shailaja Valluri ¹, Arnold Cortes ¹, Andrew Acheampong ², David F. Woodward ² and Larry A. Wheeler ²

¹ Indiana University School of Medicine, United States
² Allergan, Inc., United States

^* To whom correspondence should be addressed. E-mail: lcantor{at}iupui.edu.

Accepted 5 November 2006

Abstract

Purpose: Determine the aqueous humour concentration of the acid hydrolysis products of bimatoprost and latanoprost after a single topical dose of bimatoprost 0.03% or latanoprost 0.005% in humans.

Methods: Randomized, controlled, double-masked, prospective study. Forty-eight eyes of 48 patients scheduled for routine cataract surgery were randomized in an 8:2:2 ratio to treatment with a single 30-µL drop of bimatoprost 0.03%, latanoprost 0.005%, or placebo at 1, 3, 6, or 12 hours prior to the scheduled cataract surgery. Aqueous humour samples were withdrawn at the beginning of the surgical procedure and analyzed using HPLC-tandem mass spectrometry.

Results: Bimatoprost acid (17-phenyl trinor PGF2& [alpha]) was detected in aqueous samples at a mean concentration of 5.0 nM at hour 1, 6.7 nM at hour 3, and 1.9 nM at hour 6 after bimatoprost treatment. After latanoprost treatment, the mean concentration of latanoprost acid (13,14-dihydro-17-phenyl trinor PGF2& [alpha]) in aqueous samples was 29.1 nM at hour 1, 41.3 nM at hour 3, and 2.5 nM at hour 6. Acid metabolites were below the limit of quantitation in all samples taken 12 hours after dosing and in all samples from placebo-treated patients. None of the samples from latanoprost-treated patients contained quantifiable levels of nonmetabolized latanoprost. Nonmetabolized bimatoprost was detected in aqueous samples at a mean concentration of 6.6 nM at hour 1 and 2.4 nM at hour 3 after bimatoprost treatment.

Conclusions: Low levels of bimatoprost acid were detected in aqueous humour samples from cataract patients treated with a single dose of bimatoprost. Latanoprost acid concentrations in samples from patients treated with latanoprost were at least 6-fold higher. These results suggest that bimatoprost acid in the aqueous humour does not sufficiently account for the ocular hypotensive efficacy of bimatoprost.

Keywords: bimatoprost, glaucoma, hydrolysis, latanoprost, mechanism of action

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