TY - JOUR

T1 - Intestinal solute carriers

T2 - an overview of trends and strategies for improving oral drug absorption

AU - Steffansen, Bente

AU - Nielsen, Carsten Uhd

AU - Brodin, Birger

AU - Eriksson, André Huss

AU - Andersen, Rikke

AU - Frokjaer, Sven

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

KW - Administration, Oral

KW - Animals

KW - Drug Carriers

KW - Drug Delivery Systems

KW - Humans

KW - Intestinal Absorption

KW - Membrane Transport Proteins

M3 - Journal article

C2 - 14706808

VL - 21

SP - 3

EP - 16

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

IS - 1

ER -