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Drug Disposition Classification Systems in Discovery and Development: A Comparative Review of the BDDCS, ECCS and ECCCS Concepts

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Abstract

BDDCS, ECCS and ECCCS are compound disposition classification concepts that aim to streamline, de-risk and speed-up drug development. Although all three systems have the same purpose and are based on classifying drugs into four main categories, they have different backgrounds and contrast in their criteria. Here the details, differences and most important applications of the three systems are reviewed with particular emphasis of their roles for drug discovery and development.

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Abbreviations

BCS:

Biopharmaceutics classification system

BDDCS:

Biopharmaceutics drug disposition classification system

CLint,h :

Total hepatic intrinsic clearance

CLint,met :

Intrinsic metabolic clearance

CLint,sec :

Intrinsic biliary clearance

CLint,tot :

Total intrinsic clearance by metabolism and biliary excretion

CYP:

Cytochrome P450

D:

Clinical dose

DDI:

Drug-drug interaction

ECCS:

Extended clearance classification system

ECCCS:

EC3S extended clearance concept classification system

ECM:

Extended clearance model

fnh :

Fraction of hepatic elimination

fnmet :

Fraction of metabolic elimination

[I]u :

Unbound inhibitor concentration

IVIVC:

In vitro-in vivo correlation

IVIVE:

In vitro-in vivo extrapolation

Ki :

Inhibition constant

Kpuu :

Unbound liver-to-capillary blood concentration ratio

LLC-PK1:

Porcine kidney proximal tubule cell line

LogP:

Octanol-water partition coefficient or lipophilicity

MDCK-LE:

Canine kidney low efflux cell line

MW:

Molecular weight

OATP:

Organic anion transporting polypeptide

Qh :

Hepatic blood flow

PAMPA:

Parallel artificial membrane permeability assay

PCA:

Principal component analysis

Permpas :

Passive intestinal permeability

PK:

Pharmacokinetics

PSeff :

Sinusoidal efflux clearance or membrane permeability

PSinf,act :

Sinusoidal influx clearance or membrane permeability by active uptake

PSinf,pas :

Sinusoidal influx clearance or membrane permeability by passive diffusion

PSinf,tot :

Total sinusoidal influx clearance or membrane permeability

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ACKNOWLEDGMENTS AND DISCLOSURES

The author does not have any conflict of interest to report and is very appreciative of the outstanding students, postdoctoral fellows and scientific collaborators who contributed developing the concepts of BDDCS, ECCS as well as EC3S and their roles in drug discovery and development.

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Authors and Affiliations

  1. Department of Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, CH-4056, Basel, Switzerland

    Gian P. Camenisch

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  1. Gian P. Camenisch
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Correspondence to Gian P. Camenisch.

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Camenisch, G.P. Drug Disposition Classification Systems in Discovery and Development: A Comparative Review of the BDDCS, ECCS and ECCCS Concepts. Pharm Res 33, 2583–2593 (2016). https://doi.org/10.1007/s11095-016-2001-6

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