title: Pharmacokinetics of a self-microemulsifying drug delivery system of tacrolimus.
abstract: This study evaluated the pharmacokinetics of tacrolimus (Tac) in a novel self-microemulsifying drug delivery system (SMEDDS) for improved oral administration. SMEDDS Tac consisted of ethyl oleate as the oily phase, Solutol HS 15 as the surfactant and glycofurol as the co-surfactant and contained 0.5mg/mL tacrolimus. Blood and tissue concentrations of tacrolimus from two study groups (oral application of SMEDDS Tac and Prograf®) were determined using ELISA technique following tacrolimus administration in rats. There was no difference between area under the whole blood concentration-time curve in the SEDDM Tac group and the Prograf® group. Maximum concentrations of the drug were three times higher (P<0.05) in the SEDDM Tac group accompanied by a 3-fold earlier peak time. Elimination half-life was significantly lower in the SEDDM Tac group. Application of SMEDDS Tac increased tissue accumulation. Already after 15 min, Tac levels of small intestine, liver, kidney, spleen, heart and bone marrow were significantly higher in the SMEDDS Tac group than in the Prograf® group (P<0.05). However, the Tac concentration in the kidney was significantly lower in the SMEDDS Tac group. Formulation of SMEDDS did not affect blood-brain barrier function. The SMEDDS is a potentially useful method for a local delivery of Tac to target organs. The selection of the optimum SMEDDS Tac composition might have advantage as an alternative oral dosage form for Tac.
authors.affiliation: Department of Cardiothoracic Surgery, University Medical Center, Regensburg, Germany. marietta.suesskind-von@ukr.de
authors.forename: Marietta
authors.initials: M
authors.lastname: von Suesskind-Schwendi
authors.forename: Michael
authors.initials: M
authors.lastname: Gruber
authors.forename: Didier
authors.initials: D
authors.lastname: Touraud
authors.forename: Werner
authors.initials: W
authors.lastname: Kunz
authors.forename: Christof
authors.initials: C
authors.lastname: Schmid
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Hirt
authors.forename: Karla
authors.initials: K
authors.lastname: Lehle
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D045703:Emulsifying Agents / Q000008:administration & dosage / Q000737:chemistry; D006207:Half-Life; D009829:Oleic Acids / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013229:Stearic Acids / Q000008:administration & dosage / Q000737:chemistry; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D045703:Emulsifying Agents; D009829:Oleic Acids; D013229:Stearic Acids; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D016559:Tacrolimus; C018557:glycofurol; C033180:ethyl oleate
keywords: AUC(tot); Blood levels; FK 506; RES; Rats; SMEDDS; Tac; Tacrolimus; area under the concentration–time curve; c(max); peak level; peak time; reticuloendothelial system; self-microemulsifying drug delivery system; t(1/2); t(max); terminal elimination half-life