Latanoprost ethyl amide-d4

Latanoprost ethyl amide-d₄ (Lat-NEt-d₄) contains four deuterium atoms at the 3, 3', 4, and 4' positions. It is intended for use as an internal standard for the quantification of Lat-NEt by GC- or LC-mass spectrometry. Lat-NEt is an F-series prostaglandin (PG) analog in which the C-1 carboxyl group has been modified to an N-ethyl amide. PG esters have been shown to have ocular hypotensive activity.¹ PG N-ethyl amides were recently introduced as alternative PG ocular hypotensive prodrugs.² Although it has been claimed that PG ethyl amides are not converted to the free acids in vivo,² studies in our laboratories have shown that bovine and human corneal tissue converts the N-ethyl amides of various PGs to the free acids with a conversion rate of about 2.5 µg/g corneal tissue/hr.³ Lat-NEt would be expected to show the typical intraocular effects of Lat free acid, but with the much slower hydrolysis pharmacokinetics of the PG N-amides.

1.Bito, L.Z.Comparison of the ocular hypotensive efficacy of eicosanoids and related compoundsExperimental Eye Research38181-184(1984) 2.Woodward, D.F., Krauss, A.H.P., Chen, J., et al.The pharmacology of Bimatoprost (LumiganTM)Survey of Ophthalmology45S337-S345(2001) 3.Maxey, K.M., Johnson, J., Camras, C.B., et al.The hydrolysis of bimatoprost in corneal tissue generates a potent prostanoid FP receptor agonistSuv. Ophthalmol.47(4)S34-S40(2002)