title: Intestinal solute carriers: an overview of trends and strategies for improving oral drug absorption.
abstract: A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and/or prodrugs to these carriers in order to increasing oral bioavailability and distribution. A number of absorptive intestinal transporters are described in terms of gene and protein classification, driving forces, substrate specificities and cellular localization. When targeting absorptive large capacity membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption, and renal re-absorption, respectively. In contrast, when targeting low-capacity transporters such as vitamin transporters, dose independent saturable absorption kinetics are suggested. We thus believe that targeting drug substrates for absorptive intestinal membrane transporters could be a feasible strategy for optimizing drug bioavailability and distribution.
authors.affiliation: Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, DK-2100 Copenhagen, Denmark. bds@dfuni.dk
authors.forename: Bente
authors.initials: B
authors.lastname: Steffansen
authors.forename: Carsten Uhd
authors.initials: CU
authors.lastname: Nielsen
authors.forename: Birger
authors.initials: B
authors.lastname: Brodin
authors.forename: André Huss
authors.initials: AH
authors.lastname: Eriksson
authors.forename: Rikke
authors.initials: R
authors.lastname: Andersen
authors.forename: Sven
authors.initials: S
authors.lastname: Frokjaer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D026901:Membrane Transport Proteins