Scientific article

Biological conversion of a water-soluble prodrug of cyclosporine A

Published inEuropean journal of pharmaceutics and biopharmaceutics, vol. 67, no. 2, p. 555-561
Publication date2007

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.

  • Animals
  • Biotransformation
  • Chromatography, Ion Exchange
  • Chromatography, Liquid
  • Cyclosporine/chemistry/pharmacology
  • Cyclosporins/chemistry/pharmacokinetics
  • Hydrolysis
  • Mass Spectrometry/methods
  • Models, Chemical
  • Phosphates/chemistry
  • Prodrugs/chemistry/pharmacokinetics
  • Rabbits
  • Solubility
  • Tears/metabolism
  • Temperature
  • Water/chemistry
Citation (ISO format)
LALLEMAND, Frédéric et al. Biological conversion of a water-soluble prodrug of cyclosporine A. In: European journal of pharmaceutics and biopharmaceutics, 2007, vol. 67, n° 2, p. 555–561. doi: 10.1016/j.ejpb.2007.03.011
Main files (1)
Article (Accepted version)
ISSN of the journal0939-6411

Technical informations

Creation07/17/2009 11:37:00 AM
First validation07/17/2009 11:37:00 AM
Update time03/14/2023 3:10:23 PM
Status update03/14/2023 3:10:23 PM
Last indexation10/17/2023 2:47:02 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack