N-Desethyl Bimatoprost
[CAS# 155205-89-3]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: N-Desethyl Bimatoprost
• Synonyms: (5Z)-7-((1R,2R,3R,5S)-3,5-Dihydroxy-2-((1E,3S)-3-hydroxy-5-phenyl-1-penten-1-yl)cyclopentyl)-5-heptenamide
• Molecular Formula: C₂₃H₃₃NO₄
• Molecular Weight: 387.51
• CAS Registry Number: 155205-89-3
• SMILES: C1[C@@H]([C@@H]([C@H]([C@@H]1O)/C=C/[C@H](CCC2=CC=CC=C2)O)C/C=C\CCCC(=O)N)O

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 618.3±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 327.7±31.5 ºC (Calc.)^*
• Index of refraction: 1.615 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

N-Desethyl Bimatoprost is the primary N-de­ethyl metabolite formed after systemic absorption of bimatoprost. Although bimatoprost is administered topically via ophthalmic solution for treatment of elevated intraocular pressure or glaucoma, the compound undergoes limited systemic absorption (<1 %) and is primarily metabolised via oxidation, N-deethylation and glucuronidation. The N-desethyl metabolite results from removal of the N-ethyl side-chain of the parent molecule, yielding a molecule with a molecular mass reduced by the ethyl group (approximate molecular weight ~387.5 g/mol). It is typically isolated as a metabolite rather than a commercially used drug substance, and its presence is relevant for pharmacokinetic, excretion and toxicological profiling of bimatoprost.

Bimatoprost was first approved in 2001 for the reduction of intraocular pressure in open-angle glaucoma and ocular hypertension. After topical ocular administration, bimatoprost is absorbed through the conjunctiva and sclera, entering systemic circulation in low concentrations, where metabolism occurs. The United States Food & Drug Administration label indicates that following intravenous administration of radiolabelled bimatoprost, the parent drug was the major circulating species, but metabolites including N-deethylated forms were identified. The metabolic route of N-deethylation is part of the phase I biotransformation mediated by hepatic cytochrome P450 enzymes (among others) which remove the ethyl group of the amide nitrogen.

From an application standpoint, N-Desethyl Bimatoprost functions primarily as a biomarker of systemic exposure and metabolism of bimatoprost rather than as an active therapeutic. Its formation helps define the drug’s clearance, excretion patterns and potential metabolite-mediated effects. Because bimatoprost systemic levels are very low and the metabolite levels even lower, N-Desethyl Bimatoprost is rarely detected at significant concentrations in ocular tissues and has minimal known pharmacodynamic activity. Nonetheless, its identification reinforces the safety profile of bimatoprost by confirming metabolic pathways and elimination. Analytical methods in pharmacokinetic studies utilise mass spectrometry to quantify bimatoprost and its N-desethyl form, enabling accurate measurement of exposure, especially in special populations or in drug-interaction evaluations.

In practical research and development, understanding the formation of N-Desethyl Bimatoprost is important in drug-metabolism studies, regulatory submissions and formulation development of bimatoprost ophthalmic preparations. The low systemic exposure and rapid elimination (half-life ~45 minutes after intravenous administration of bimatoprost) indicate that neither the parent drug nor the metabolite accumulates significantly in systemic circulation with topical dosing. Thus, N-desethylation is one of several minor metabolic routes that support the favourable safety profile of the therapeutic regimen. Future investigations may assess whether any rare individuals with altered P450 activity produce differing amounts of the N-desethyl metabolite or whether that impacts ocular versus systemic responses to bimatoprost therapy.

References

Cantor LB (2005) Clinical pharmacology of bimatoprost. *Expert Opinion on Drug Metabolism & Toxicology* 1(1) 151–157. DOI: 10.1517/17425255.1.1.151

FDA (2012) LUMIGAN® (bimatoprost ophthalmic solution) prescribing information. U.S. Food & Drug Administration. Link