WorldCat Identities

Attivi, David (1970-....).

Works: 3 works in 3 publications in 2 languages and 4 library holdings
Roles: Other, Author
Publication Timeline
Most widely held works by David Attivi
The effect of intravenous isosorbide dinitrate in acute decompensated heart failure in hospital by Jérémy Chambord( )

1 edition published in 2017 in English and held by 2 WorldCat member libraries worldwide

Mise en forme et amélioration de la biodisponibilité d'un anticancéreux destiné à la voie orale : exemple du mitotane by David Attivi( )

1 edition published in 2010 in French and held by 1 WorldCat member library worldwide

Mitotane or o, p'-DDD is a organochlorine drug, very slightly soluble in water. It is used in the treatment of non resectable and metastasized adrenocortical carcinoma (Lysodren®). In therapy, to achieve therapeutic plasma level, high cumulative doses of mitotane were usually used during 3-5 months. This regimen causes gastrointestinal and neuromuscular side effects and make patients to be less compliants.The main objective of this work is to developp differents formulations of mitotane in order to improve the relative bioavailability when compared with conventional form Lysodren®. To shorten this equilibration time and reduce side effects, it's necessary to develop a new formulation. In order to increase mitotane solubility and make it more bioavailable, we encapsulated mitotane in polymeric particles and microemulsions.We prepared nanocapsules with biodegradable polymers (poly-epsilon-caprolactone) (PCL) and an association of PCL and non-biodegradable polymers (Eudragit®RL). We have also prepared PCL microparticles and a Self Microemulsifying Drug Delivery System or SMEDDS.Nanocapsules and microparticles diameters were respectively 300 nm and 40 to 76 µm. The zeta potential is negative for PCL particles wheras particles combining PCL and Eudragit®RL polymers exhibited positive zêta potential. For microemulsions, we investigated by constructing ternary phase diagrams and choosing the optimal formulation consisted of a mixture of Capryol®, Tween® 20 and Cremophor® EL (33, 33, 33%) with an emulsion diameter of 40 nm. The release of mitotane from SMEDDS and particles was higher and faster than from the conventional form Lysodren®.Pharmacokinetics after single-dose of oral mitotane formulations (100 mg/kg) in rabbits showed a 339% increase of relative bioavailability with microemulsions, 195% with the nanocapsules and 187% with the microparticles. Caco-2 cell culture showed a complete absorption of mitotane after 4h with microemulsions. For microparticles and nanocapsules, 50 and 45% of the initial dose, were respectively absorbed by Caco-2 cells. Caco-2 cells evaluation confirmed the low absorption of the mitotane powder (10%). Finally, Ussing chamber showed that microemulsions pass through the intestinal barrier 5 times higher than a solution of mitotane. In conclusion, microemulsions showed improvement of bioavailability of mitotane by a factor 3 in rabbits and could allow cost effective production. Microemulsions are a real alternative to Lysodren® which is currently available on the European market
Audience Level
Audience Level
  Kids General Special  
Audience level: 0.96 (from 0.96 for Mise en pl ... to 0.97 for The effect ...)