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
SN - 0928-0987
VL - 21
SP - 3
EP - 16
JO - Norvegica Pharmaceutica Acta
JF - Norvegica Pharmaceutica Acta
IS - 1
ER -