title: Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase.
abstract: We investigated the effect of esterase on rectal absorption in the rat of itazigrel using polysorbate 80 (PS-80) micelle as a vehicle to overcome the poor aqueous solubility of itazigrel. The itazigrel formulation prepared with PS-80 increased the absorption compared with a 0.25% carmellose sodium suspension, probably by supplying the itazigrel solute to keep a high concentration at the epithelial surface. When esterase was co-administered with the formulations containing PS-80, the absorption of itazigrel from rat rectum was accelerated further, by rapid release of itazigrel from the micelle vehicle after enzymatic degradation of the PS-80 micelle.
authors.affiliation: Upjohn Tsukuba Research Laboratories, Upjohn Pharmaceuticals Limited, Ibaraki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: A C
authors.initials: AC
authors.lastname: Shah
authors.forename: T
authors.initials: T
authors.lastname: Nishihata
mesh_terms: D000042:Absorption / Q000187:drug effects; D000285:Administration, Rectal; D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004347:Drug Interactions; D004950:Esterases / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008823:Micelles; D011136:Polysorbates / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D005343:Fibrinolytic Agents; D008823:Micelles; D011136:Polysorbates; D013844:Thiazoles; D004950:Esterases; C035025:itazigrel