Horse metabolism and the photocatalytic process as a tool to identify metabolic products formed from dopant substances: the case of sildenafil.

The research article describes a study on horses treated with a medication called sildenafil. Researchers identified and analyzed the metabolic products of sildenafil in these horses’ urine and blood samples, comparing them with expected products identified in a lab simulation using a photocatalytic process.

Methodology

• The research begins with a simulative laboratory study, simulating the metabolic process with a photocatalytic process. A photocatalyst, titanium dioxide, was used to identify possible main and secondary transformation products of sildenafil.
• Following the simulation, two horses were treated with sildenafil, an erectile dysfunction drug also used in pulmonary hypertension. Their urine and blood samples were then collected and analyzed.
• The HPLC/HRMS(n) technique, a method of identifying compounds based on their mass and charge, was used to characterize the products formed.

Results

• The main intermediates identified in the photocatalytic process experiment were found to be the same as the major metabolites of sildenafil found in the horses and previously studied rats. This may suggest that the photocatalytic process with titanium dioxide deliver results consistent with in vivo metabolism.
• In terms of horse metabolism specifically, sildenafil and its demethylated product (UK 103,320) were identified and quantified in blood samples, while sildenafil propyloxide, de-ethyl, and demethyl sildenafil, were quantified in the urine.
• In addition to these metabolites, more oxidized species were also found in both urine and plasma samples of the treated animals. These products were also formed in the earlier photocatalytic process using titanium dioxide and indicate further oxidation and hydroxylation of sildenafil during metabolism.

Implications

• The study shows a correspondence between the metabolic products predicted by the photocatalytic process and what was found in vivo, highlighting the utility of the photocatalytic technique to predict metabolic products of drugs.
• The identification of sildenafil metabolites in horses has potential implications for further metabolism studies and for understanding the effects of the medication in non-human species. It may also be of relevance to regulatory authorities in horse racing, for example, where certain substances might be prohibited.