Skip to main content
SpringerLink
Log in

An Overview of Transporter Information in Package Inserts of Recently Approved New Molecular Entities

  • Commentary
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abbreviations

ABC:

ATP-binding cassette

ADME:

absorption, distribution, metabolism, and excretion

BCRP:

breast cancer resistance protein

BSEP:

bile salt export pump

DDI:

drug-drug interaction

EMA:

European Medicines Agency

FDA:

Food and Drug Administration

ITC:

International Transporter Consortium

MATE:

multidrug and toxic compound extrusion

MCT:

monocarboxylate transporter

MRP:

multi-drug resistance-associated protein

NET:

norepinephrine transporter

NCTP:

Na+-taurocholate cotransporting polypeptide

NDA:

new drug application

NME:

new molecular entity

OAT:

organic anion transporter

OATP:

organic anion transporting polypeptide

OCT:

organic cation transporter

P-gp:

P-glycoprotein

PI:

package insert

PK:

pharmacokinetics

PD:

pharmacodynamics

SLC:

solute carrier

VMAT:

vesicular monoamine transporter

References

  1. Giacomini KM, Huang SM, Tweedie DJ, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215–36.

    Article  PubMed  CAS  Google Scholar 

  2. Huang SM, Zhang L, Giacomini KM. The International Transporter Consortium (ITC): a collaborative group of scientists from academia, industry and FDA. Clin Pharm Ther. 2010;87(1):32–6.

    Article  Google Scholar 

  3. Food and Drug Administration Meeting of the Advisory Committee for Pharmaceutical Science and Clinical Pharmacology March 17, 2010. Available from: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/ucm201700.htm. [Last accessed: 2012 March 29].

  4. Guidance for Industry Drug Interaction Studies—Study Design, Data Analysis, Implications for Dosing, and Labeling Recommendations. Available from: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm064982.htm. [Last accessed: 2012 March 29].

  5. European Medicines Agency’s Scientific Guideline on the Investigation of Drug Interactions. 2012 June 21. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf. [Last accessed: 2012 March 29].

  6. FDA Drug Development and Drug Interaction Website. Available from: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm [Last accessed: 2012 March 29].

  7. New Requirements for Prescribing Information. Available from: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm084159.htm. [Last accessed: 2012 March 29].

  8. Guidance for Industry Clinical Pharmacology Section of Labeling for Human Prescription Drug and Biological Products—Content and Format . Available from: http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm065010.htm. [Last accessed: 2012 March 29].

  9. Zhang L, Zhang Y, Strong J, Reynolds KS, Huang S-M. A regulatory viewpoint on transporter-based drug interactions. Xenobiotica. 2008;38(7–8):709–24.

    Article  PubMed  CAS  Google Scholar 

  10. Agarwal S, Arya V, Zhang L. Review of P-gp inhibition data in recently approved new drug applications: Utility of the proposed [I1]/IC50 and [I2]/IC50 criteria in the P-gp decision tree. J Clin Pharmacol. 2012 Feb 7 [Epub ahead of print].

  11. Hua WJ, Hua WX, Fang HJ. The role of OATP1B1 and BCRP in pharmacokinetics and DDI of novel statins. Cardiovasc Ther 2011 [Epub ahead of print].

  12. Shitara Y, Takeuchi K, Nagamatsu Y, Wada S, Sugiyama Y, Horie T. Long-lasting inhibitory effects of cyclosporin A, but not tacrolimus, on OATP1B1- and OATP1B3-mediated uptake. Drug Metab Pharmacokinet. 2012 Jan 13. [Epub ahead of print]

  13. Gupta A, Dai Y, Vethanayagam RR, Hebert MF, Thummel KE, Unadkat JD, Ross DD, Mao Q. Cyclosporin A, tacrolimus and sirolimus are potent inhibitors of the human breast cancer resistance protein (ABCG2) and reverse resistance to mitoxantrone and topotecan. Cancer Chemother Pharmacol. 2006;58(3):374–83.

    Article  PubMed  CAS  Google Scholar 

  14. Vaidyanathan S, Camenisch G, Schuetz H, et al. Pharmacokinetics of the oral direct renin inhibitor aliskiren in combination with digoxin, atorvastatin, and ketoconazole in healthy subjects: the role of P-glycoprotein in the disposition of aliskiren. J Clin Pharmacol. 2008;48(11):1323–38.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments and Disclosures

The authors wish to thank Dr. Shiew-Mei Huang for her critical review of this manuscript, members of the Office of Clinical Pharmacology (OCP) Transporter Scientific Interest Group (SIG), Hari Krishna Ananthula (an ORISE Fellow), as well as review staff members in OCP, for their support of this project.

 

Part of this commentary was presented as posters at the American College of Clinical Pharmacology (ACCP) Annual Meeting in Baltimore, MD, in September 2010 and the American Association for Pharmaceutical Scientists (AAPS) Transporter Workshop in North Bethesda, MD in March 2011.

 

The views expressed in this article are those of the authors and do not necessarily reflect the official views of the FDA. The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Office of Clinical Pharmacology, Office of Translational Sciences Center for Drug Evaluation and Research U.S. Food and Drug Administration, Building 51, Room 3139, White Oak 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

    Sheetal Agarwal

  2. Office of Clinical Pharmacology, Office of Translational Sciences Center for Drug Evaluation and Research U.S. Food and Drug Administration, Building 51, Room 2131, White Oak 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

    Leslie Chinn

  3. Office of Clinical Pharmacology, Office of Translational Sciences Center for Drug Evaluation and Research U.S. Food and Drug Administration, Building 51, Room 3106, White Oak 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

    Lei Zhang

Authors
  1. Sheetal Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leslie Chinn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lei Zhang.

Electronic Supplementary Materials

Below is the link to the electronic supplementary material.

Supplemental Table I

(DOC 36.5 kb)

Supplemental Figure 1

(DOC 24 kb)

Supplemental Figure 2

(DOC 31 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Agarwal, S., Chinn, L. & Zhang, L. An Overview of Transporter Information in Package Inserts of Recently Approved New Molecular Entities. Pharm Res 30, 899–910 (2013). https://doi.org/10.1007/s11095-012-0924-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-012-0924-0

KEY WORDS

Search

Navigation