Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Sep;26(9):2039-54.
doi: 10.1007/s11095-009-9924-0. Epub 2009 Jun 30.

The role of transporters in the pharmacokinetics of orally administered drugs

Sarah Shugarts  1 , Leslie Z Benet
Affiliations
Review

The role of transporters in the pharmacokinetics of orally administered drugs

Sarah Shugarts et al. Pharm Res. 2009 Sep.

Abstract

Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Enterocyte with intestinal uptake (green) and efflux (blue) transporters. Multidrug resistance protein (MDR), Multidrug resistance associated protein (MRP), Breast cancer resistance protein (BCRP), Monocarboxylate transporter protein (MCT), Peptide transport protein (PEPT), Organic anion transporting polypeptide (OATP), Organic cation transporter (OCT), apical sodium-dependent bile acid transporter (ASBT), Concentrative nucleotide transporter (CNT), Electroneutral organic cation transporter (OCTN), Equilibrative nucleoside transporter (ENT). Adapted from Custodio et al. (58).
Fig. 2
Fig. 2
Hepatocyte with hepatic uptake (green) and efflux (blue) transporters. Multidrug resistance associated protein (MRP), Organic cation transporter (OCT), Organic anion transporter (OAT), Organic anion transporting polypeptide (OATP), sodium-taurocholate cotransporting polypeptide (NTCP), P-glycoprotein (Pgp), Multidrug resistance protein (MDR), Breast cancer resistance protein (BCRP), Bile salt export pump (BSEP). Adapted from Custodio et al. (58).
Fig. 3
Fig. 3
The Biopharmaceutics Classification System (BCS) as put forth by Amidon et al. (6) and defined by the FDA (21).
Fig. 4
Fig. 4
Biopharmaceutics Drug Disposition Classification System (BDDCS) as put forth by Wu and Benet (5).
Fig. 5
Fig. 5
Transporter effects predicted by BDDCS following oral dosing.
Fig. 6
Fig. 6
Predicted high fat meal effects by BDDCS classification after Wu and Benet (5).
See this image and copyright information in PMC

References

    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '990323', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/990323/'}]}
    2. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in chinese hamster ovary cell mutants. Biochim. Biophys. Acta. 1976;455:152–162. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '10706193', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/10706193/'}]}
    2. Fromm MF. P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs. Int. J. Clin. Pharmacol. Ther. 2000;38(2):69–74. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '12750437', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/12750437/'}]}
    2. Landowski CP, Sun D, Foster DR, Menon SS, Barnett JL, Welage LS, et al. Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. J. Pharmacol. Exp. Ther. 2003;306(2):778–786. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '15618657', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/15618657/'}]}
    2. Mizuno N, Sugiyama Y. Drug transporters: their role and importance in the selection and development of new drugs. Drug Metab. Pharmacokinet. 2002;17(2):93–108. - PubMed
    1. {'text': '', 'ref_index': 1, 'ids': [{'type': 'PubMed', 'value': '15771225', 'is_inner': True, 'url': 'https://pubmed.ncbi.nlm.nih.gov/15771225/'}]}
    2. Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm. Res. 2005;22(1):11–23. - PubMed

Publication types

Substances