Biological conversion of a water-soluble prodrug of cyclosporine A
| Autor: | Gérard Hopfgartner, Emmanuel Varesio, Robert Gurny, Frédéric Lallemand, Leila Bossy, Olivia Felt-Baeyens |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Phosphatase
Pharmaceutical Science Prodrugs/chemistry/pharmacokinetics Cyclosporins Mass Spectrometry Phosphates chemistry.chemical_compound Hydrolysis Biotransformation Tears/metabolism Liquid chromatography–mass spectrometry Enzymatic hydrolysis Phosphates/chemistry Animals Prodrugs Mass Spectrometry/methods chemistry.chemical_classification ddc:615 Chromatography Chemistry Temperature Water General Medicine Prodrug Phosphate Chromatography Ion Exchange Enzyme Models Chemical Solubility Water/chemistry Cyclosporins/chemistry/pharmacokinetics Tears Cyclosporine/chemistry/pharmacology Cyclosporine Rabbits Biotechnology Chromatography Liquid |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics, Vol. 67, No 2 (2007) pp. 555-61 |
| ISSN: | 0939-6411 |
| Popis: | UNIL088 is a water-soluble prodrug of cyclosporine A (CsA) designed for topical ocular delivery. The pro-moiety is grafted via an ester function to CsA and the solubilizing group is a phosphate ion. The aim of this study was to elucidate the conversion mechanisms by which UNIL088 generates CsA. UNIL088 was incubated in rabbit tears at physiological temperature to study its enzymatic and chemical conversion, respectively. Metabolites and intermediates were identified using a quadrupole-time of flight (QqTOF) mass spectrometer, which allowed biotransformation pathways to be deduced. Conversion is activated by the chemical or enzymatic hydrolysis of the terminal ester function of the pro-moiety, leading to the phospho-serine-sarcosine-cyclosporine A that spontaneously converts into CsA. In addition to the main biotransformation pathway, a secondary reaction involved hydrolysis of the phosphate ester group of the pro-moiety, probably by phosphatases present in tears. |
| Databáze: | OpenAIRE |
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