title: Bioavailability of hop-derived iso-α-acids and reduced derivatives.
abstract: Iso-α-acids (IAA) and their reduced derivatives (dihydro-iso-α-acids (DHIAA) and tetrahydro-iso-α-acids (THIAA)) have been administered to Caco-2 cell monolayers (30, 60, and 120 μM) to investigate epithelial transport, in both absorptive and secretive directions. In addition, 25 mg kg(-1) IAA, DHIAA, and THIAA were applied to New Zealand white rabbits (±3-3.5 kg) in a single intravenous and oral dose. The most important pharmacokinetic parameters (C(max), t(max), half life, clearance, and AUC(0-∞)) and the absolute bioavailability were determined for each class of hop acid. The results from the in vitro Caco-2 study of IAA, DHIAA, and THIAA, showed a higher membrane permeability for IAA and THIAA, both in absorptive (P(appAB) range 1.6-5.6 × 10(-6) cm s(-1)) and secretive directions (P(appBA) range 5.7-16.3 × 10(-6) cm s(-1)), when compared to DHIAA. Factors limiting transport of DHIAA could include phase II metabolism. After oral and i.v. dosing to New Zealand white rabbits, the absolute bioavailability for IAA was determined to be 13.0%. The reduced derivatives reached higher bioavailabilities with 28.0% for DHIAA and 23.0% for THIAA. The area under curve AUC(0-∞) upon oral gavage for DHIAA and THIAA was 70.7 ± 48.4 μg h ml(-1) and 57.4 ± 9.0 μg h ml(-1), respectively, while that for IAA was 10.6 ± 5.3 μg h ml(-1). Phase I metabolism was indicated as the main factor limiting the bioavailability of IAA. Bioavailability of DHIAA is mostly influenced by phase-II metabolism as shown by enzymatic hydrolysis of plasma samples upon administration of DHIAA.
authors: UGent-Ghent University, Faculty of Pharmaceutical Sciences, Laboratory of Pharmacognosy and Phytochemistry, Harelbekestraat 72, B-9000 Ghent, Belgium.
authors: Ko
authors: K
authors: Cattoor
authors: Jean-Paul
authors: JP
authors: Remon
authors: Koen
authors: K
authors: Boussery
authors: Jan
authors: J
authors: Van Bocxlaer
authors: Marc
authors: M
authors: Bracke
authors: Denis
authors: D
authors: De Keukeleire
authors: Dieter
authors: D
authors: Deforce
authors: Arne
authors: A
authors: Heyerick
mesh_terms: D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D053138:Cyclohexenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D003517:Cyclopentanes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D007408:Intestinal Absorption; D011817:Rabbits; D013729:Terpenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D053138:Cyclohexenes; D003517:Cyclopentanes; D013729:Terpenes; C081209:isohumulone; C007966:humulon