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Levels of bimatoprost acid in the aqueous humour after bimatoprost treatment of patients with cataract

Louis B Cantor¹, Joni Hoop¹, Darrell Wudunn¹, Chi-Wah Yung¹, Yara Catoira¹, Shailaja Valluri¹, Arnold Cortes¹, Andrew Acheampong², David F Woodward² and Larry A Wheeler²

¹ Indiana University, Indianapolis, Indiana, USA
² Allergan, Irvine, California, USA

Correspondence to:
Correspondence to:
Professor L B Cantor
Glaucoma Services, Department of Ophthalmology, Indiana University Medical Center, Indianapolis, IN 46202, USA; lcantor{at}iupui.edu

Aim: To 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: Randomised, controlled, double-masked, prospective study. 48 eyes of 48 patients scheduled for routine cataract surgery were randomised 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 h before the scheduled cataract surgery. Aqueous humour samples were withdrawn at the beginning of the surgical procedure and analysed using high-performance liquid chromatography–tandem mass spectrometry.

Results: Bimatoprost acid (17-phenyl trinor prostaglandin F2) 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 prostaglandin F2) 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 h after dosing and in all samples from placebo-treated patients. None of the samples from latanoprost-treated patients contained quantifiable levels of non-metabolised latanoprost. Non-metabolised 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 patients with cataract treated with a single dose of bimatoprost. Latanoprost acid concentrations in samples from patients treated with latanoprost were at least sixfold higher. These results suggest that bimatoprost acid in the aqueous humour does not sufficiently account for the ocular hypotensive efficacy of bimatoprost.

Abbreviations: BLQ, below the limit of quantitation; d4, tetradeuterated; d5, pentadeuterated; IOP, intraocular pressure; HPLC–MS/MS, high-performance liquid chromatography–tandem mass spectrometry; PGF2, prostaglandin F2

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This article has been cited by other articles:

• Camras, C B, Sharif, N A, Wax, M B, Stjernschantz, J (2008). Bimatoprost, the prodrug of a prostaglandin analogue. Br. J. Ophthalmol. 92: 862-863 [Full Text]  
• Cantor, L B (2008). Author's reply. Br. J. Ophthalmol. 92: 863-864 [Full Text]