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Membrane Transporters in ADME

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Transporters in Drug Development

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 7))

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Abstract

Transporter-mediated absorption or efflux of drug compounds across tissue barriers may affect drug ADME properties. This is exemplified in the present chapter, where we demonstrate how the intestinal proton-coupled amino acid transporter PAT1 may act as a mediator of intestinal gaboxadol absorption. We also discuss how organic anions may be substrates for multiple intestinal transporters. The role of the apical proton co-transporter OATP2B1 and the basolateral facilitative OSTα/β transporter in absorptive and exsorptive transport of the organic anion model substrate E1S is treated in detail.

Distribution of drug compounds across the blood–brain barrier does rely on transporters to a large extent, and we describe the challenges of developing in vitro methods which may predict drug distribution to the CNS.

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Abbreviations

δ-ALA:

δ-Aminolevulinic acid

ABC:

ATP-binding cassette

ADME:

Absorption, distribution, metabolism, and excretion

ASBT:

Apical sodium-dependent bile acid transporter

BBB:

Blood–brain barrier

BCRP:

Breast cancer resistance protein

BSEP:

Bile salt export pump

Caco-2:

Colorectal adenocarcinoma cells

DDI:

Drug–drug interactions

DHEAS:

Dihydroepiandrosterone-3-sulfate

E1S:

Estrone-1-sulfate

EMA:

European Medicines Agency

FDA:

US Food and Drug Administration

K m :

Michaelis constant

l-Pro:

l-Proline

l-Trp:

l-Tryptophan

MATE:

Multidrug and toxin extrusion

MCT:

Monocarboxylate transporter

MRP:

Multidrug resistance protein

NCE:

New chemical entity

NTCP:

Na+ taurocholate cotransporting polypeptide (human)

NVU:

Neurovascular unit

OAT:

Organic anion transporter

OATP:

Organic anion transporting polypeptide

OST:

Organic solute transporter

P APP :

Apparent permeability

PAT:

Proton-coupled amino acid transporter

PEPT:

Proton-coupled di-/tripeptide transporter

P UP :

Uptake/influx permeability

SLC:

Solute carrier

SLCO:

Solute carrier organic anion

TCA:

Taurocholic acid

TJ:

Tight junctions

V max :

Maximal transport rate

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Authors and Affiliations

  1. Faculty of Health and Medical Sciences, Department of Pharmacy, Drug Transporters in ADME, University of Copenhagen, 2 Universitetsparken, Copenhagen, 2100, Denmark

    Bente Steffansen M.Sc.(Pharm), Ph.D., Carsten Uhd Nielsen & Birger Brodin

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  1. Bente Steffansen M.Sc.(Pharm), Ph.D.
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  2. Carsten Uhd Nielsen
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  3. Birger Brodin
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Correspondence to Bente Steffansen M.Sc.(Pharm), Ph.D. .

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Editors and Affiliations

  1. The University of Tokyo Graduate School of Pharmac. Sciences, Tokyo, Japan

    Yuichi Sugiyama

  2. Pharma, Drug Transporters in ADME Department of Pharmacy, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark

    Bente Steffansen

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Steffansen, B., Nielsen, C.U., Brodin, B. (2013). Membrane Transporters in ADME. In: Sugiyama, Y., Steffansen, B. (eds) Transporters in Drug Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8229-1_1

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