Reference : Pharmacokinetic study of a new synthetic MMP inhibitor (Ro 28-2653) after IV and oral...
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/11901
Pharmacokinetic study of a new synthetic MMP inhibitor (Ro 28-2653) after IV and oral administration of cyclodextrin solutions
English
Piette, Marie mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique >]
Evrard, Brigitte mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique >]
Frankenne, Francis [ > > ]
Chiap, Patrice mailto [Université de Liège - ULg > Département de pharmacie > Analyse des médicaments >]
Bertholet, P. [> > > >]
Castagne, Delphine mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique et magistrale >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
Delattre, Luc mailto [Université de Liège - ULg > Département de pharmacie > Département de pharmacie >]
Piel, Géraldine mailto [Université de Liège - ULg > Département de pharmacie > Pharmacie galénique et magistrale >]
Jun-2006
European Journal of Pharmaceutical Sciences
Elsevier Science
28
3
189-195
Yes (verified by ORBi)
International
0928-0987
Amsterdam
The Netherlands
[en] matrix metalloproteinase inhibitor ; Ro 28-2653 ; cycloclextrin ; ternary inclusion complexes ; bioavailability
[en] Ro 28-2653 (5-biphenyl-4-yl-5-[4-(4-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6-trione) is a new synthetic inhibitor of matrix metalloproteinases (MMPs) with a high selectivity towards MMP2, MMP9 and membrane type 1-MMP. It has been shown that cyclodextrins (CDs) are able to form inclusion complexes with Ro 28-2653 and to increase its aqueous solubility. The aim of this study is to demonstrate that an increase in Ro 28-2653 solubility, via ternary complex formation, can lead to an increase in the oral bioavailability of this drug. This study shows that a synergistic effect exists between hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and L-lysine. The use of this multicomponent system enabled the preparation of oral and intravenous solutions of Ro 28-2653. In vivo evaluation of the oral solution of the inclusion complex of Ro 28-2653 in comparison with a suspension of the same uncomplexed drug showed a significant (p < 0.05) increase in absolute bioavailability. The area under curve (AUC) and the peak serum concentration (C-max) were approximately 10 times higher than those obtained with the suspension, while the time (T-max) to reach C-max was reduced. Moreover, in vivo administration of Ro 28-2653 solutions highlighted some information about the pharmacokinetic behavior of Ro 28-2653: a long biologic half-life (about 15.5 h) and a small overall volume of distribution (81). (c) 2006 Elsevier B.V. All rights reserved.
http://hdl.handle.net/2268/11901
10.1016/j.ejps.2006.01.011

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