title: Comparison of the intestinal absorption and bioavailability of γ-tocotrienol and α-tocopherol: in vitro, in situ and in vivo studies.
abstract: The aim of this work was to compare the intestinal absorption kinetics and the bioavailability of γ-tocotrienol (γ-T3) and α-tocopherol (α-Tph) administered separately as oil solutions to rats in vivo. Also, to explain the significant difference in the oral bioavailability of the compounds: (1) the release profiles using the dynamic in vitro lipolysis model, (2) the intestinal permeability and (3) carrier-mediated uptake by Niemann-Pick C1-like 1 (NPC1L1) transporter were examined. Absolute bioavailability studies were conducted after oral administration of γ-T3 or α-Tph prepared in corn oil to rats. In situ rat intestinal perfusion with ezetimibe (a NPC1L1 inhibitor) was performed to compare intestinal permeability. The in vitro interaction kinetics with NPC1L1 was examined in NPC1L1 transfected cells. While the in vitro release studies demonstrated a significantly higher release rate of γ-T3 in the aqueous phase, the oral bioavailability of α-Tph (36%) was significantly higher than γ-T3 (9%). Consequent in situ studies revealed significantly higher intestinal permeability for α-Tph compared with γ-T3 in rats. Moreover, the NPC1L1 kinetic studies demonstrated higher Vmax and Km values for α-Tph compared with γ-T3. Collectively, these results indicate that intestinal permeability is the main contributing factor for the higher bioavailability of α-Tph. Also, these results emphasize the potentially important role of intestinal permeability in the bioavailability of γ-T3, suggesting that enhancing its permeability would increase its oral bioavailability.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
authors.forename: Bilal S
authors.initials: BS
authors.lastname: Abuasal
authors.forename: Hisham
authors.initials: H
authors.lastname: Qosa
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sylvester
authors.forename: Amal
authors.initials: A
authors.lastname: Kaddoumi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001384:Azetidines / Q000494:pharmacology; D001682:Biological Availability; D003314:Corn Oil / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D000069438:Ezetimibe; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D015394:Molecular Structure; D010477:Perfusion; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D024504:gamma-Tocopherol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D001384:Azetidines; D004337:Drug Carriers; D026901:Membrane Transport Proteins; C482444:NPC1L1 protein, rat; D003314:Corn Oil; D024504:gamma-Tocopherol; D000069438:Ezetimibe; D024502:alpha-Tocopherol