Conversion of cyclosporine A prodrugs in human tears vs rabbits tears

Lallemand, Frédéric; Felt-Baeyens, Olivia; Rudaz, Serge; Hamel, A R; Hubler, F; Wenger, R; Mutter, M; Besseghir, K; Gurny, Robert

doi:10.1016/j.ejpb.2004.07.002

Scientific article

English

Conversion of cyclosporine A prodrugs in human tears vs rabbits tears

Contributors

Lallemand, Frédéric; Felt-Baeyens, Olivia; Rudaz, Serge

; Hamel, A R; Hubler, F; Wenger, R; Mutter, M; Besseghir, K; Gurny, Robert

Published in

European journal of pharmaceutics and biopharmaceutics, vol. 59, no. 1, p. 51-56

Publication date

2005

Abstract

The aim of this study was to evaluate the rate and mechanism of conversion of two water-soluble prodrugs of cyclosporine A (CsA) intended for topical delivery to the eye. The new molecules were designed according to the double prodrug concept: a solubilizing moiety was grafted onto CsA via an ester function, which could be hydrolysed via a two-step process (enzymatic and chemical). Prodrug solutions were prepared extemporaneously in an isotonic and neutral aqueous medium compatible with ophthalmic use. The rates of conversion into the parent molecule were determined by incubating the prodrugs in fresh rabbit or human tears or in a phosphate buffer solution (PBS) at pH 7.4. Both prodrugs were converted into CsA within the first minute in the presence of rabbit tears with rate constants of k=5.9x10(-3)min(-1) and k=3.8x10(-3)min(-1), respectively, for UNIL088 and UNIL089, whereas chemical conversion in PBS was negligible (k=0.5x10(-3)min(-1) for both molecules). Incubation of UNIL088 in human tears showed a significantly high conversion rate. It is concluded that the developed double prodrugs underwent a bioconversion in physiological media and thus represent promising candidates for topical delivery of CsA to the eye.

Keywords

Animals
Cyclosporine/chemistry/pharmacokinetics
Humans
Prodrugs/chemistry/pharmacokinetics
Rabbits
Tears/metabolism

UNIGE affiliation entities

Faculté des sciences / Section des sciences pharmaceutiques

Citation (ISO format)

LALLEMAND, Frédéric et al. Conversion of cyclosporine A prodrugs in human tears vs rabbits tears. In: European journal of pharmaceutics and biopharmaceutics, 2005, vol. 59, n° 1, p. 51–56. doi: 10.1016/j.ejpb.2004.07.002

Article (Published version)

Identifiers

PID : unige:84375
DOI : 10.1016/j.ejpb.2004.07.002
PMID : 15567301

Journal ISSN

0939-6411

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Conversion of cyclosporine A prodrugs in human tears vs rabbits tears

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

Citation (ISO format)

Main files (1)

Identifiers

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation