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BDDCS Applied to Over 900 Drugs

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Abstract

Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD 7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and experimentally measured values. We discuss the potential use of BDDCS to estimate the disposition characteristics of novel chemicals (new molecular entities) in the early stages of drug discovery and development. Transporter effects in the intestine and the liver are not clinically relevant for BDDCS class 1 drugs, but potentially can have a high impact for class 2 (efflux in the gut, and efflux and uptake in the liver) and class 3 (uptake and efflux in both gut and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N = 53 compared with over 200 each in classes 1–3). The influence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail.

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Acknowledgments

The authors were supported in part in preparation of the five tables and this manuscript by NIH grants GM-61390, GM-75900 and GM-90457 (LZB), and by GM-095952, MH-084690, and CA-118100 (TIO). We thank Molecular Discovery Ltd. and Professor Cruciani for the VolSurf+ suite license.

Supporting Info Available

An excel file is available as supporting info containing the following data for the 927 drugs dataset: name, BDDCS class, max dose strength value, max dose strength unit, formulation, route, measured solubility, dose number, % excreted unchanged in urine, MW drug, MW solution, pDose, measured LogS molar, measured LogP, measured LogD 7.4, ALOGPS 2.1 solubility, cDose Number (ALOGPS based), minVSLgS, cDose Number (minVSLgS based), cLogP, HBA,HBD, PSA, and violations to Rules of Five. Definitions for the terms used only in the supporting info file may be found at the end of that data set. In addition, box plots of minVSLgS, ALOGPS 2.1 solubility, MLogP, cLogP, MW, PSA parameters against BDDCS are provided.

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Authors and Affiliations

  1. Department of Bioengineering & Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, 533 Parnassus Avenue, Room U-68, San Francisco, California, 94143-0912, USA

    Leslie Z. Benet & Fabio Broccatelli

  2. Laboratory of Chemometrics, Department of Chemistry, University of Perugia, Via Elce di Sotto, 10, 60123, Perugia, Italy

    Fabio Broccatelli

  3. Sunset Molecular Discovery LLC, 1704 B Llano Street, Suite 324, Santa Fe, New Mexico, 87505, USA

    Tudor I. Oprea

  4. Department of Biochemistry and Molecular Biology, Division of Biocomputing, University of New Mexico School of Medicine, Mail stop code 116145, Albuquerque, New Mexico, 87131, USA

    Tudor I. Oprea

  5. Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet, Building 208, Lyngby, 2800, Denmark

    Tudor I. Oprea

Authors
  1. Leslie Z. Benet
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  2. Fabio Broccatelli
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Correspondence to Leslie Z. Benet.

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Benet, L.Z., Broccatelli, F. & Oprea, T.I. BDDCS Applied to Over 900 Drugs. AAPS J 13, 519–547 (2011). https://doi.org/10.1208/s12248-011-9290-9

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