A hierarchical QSAR model for urinary excretion of drugs in humans as a predictive tool for biotransformation

QSAR and Combinatorial Science

Volumn 22, Issue 2, 2003, Pages 263-273

  Manga, Na'ngono ^a   Duffy, Judith C ^a   Rowe, Philip H ^a   Cronin, Mark T D ^a  

^a LIVERPOOL JOHN MOORES UNIVERSITY   (United Kingdom)

Author keywords

Bioavailabililty; Biotransformation; FIRM; Linear discriminant analysis; Metabolism; QSAR; QSPKR; Recursive Partitioning

Indexed keywords

COMPUTATIONAL CHEMISTRY; DECISION TREES; DISCRIMINANT ANALYSIS; DRUG DOSAGE; PHYSIOLOGY;

BIOAVAILABILILTY; BIOTRANSFORMATION; FIRM; LINEAR DISCRIMINANT ANALYZE; PREDICTIVE TOOLS; QSAR; QSAR MODEL; QSPKR; RECURSIVE PARTITIONING; URINARY EXCRETION;

METABOLISM;

ACEBUTOLOL; ACETYLSALICYLIC ACID; ALPRAZOLAM; AMANTADINE; AMFEBUTAMONE; AMILORIDE; ANTIBIOTIC AGENT; BETAXOLOL; BUSULFAN; CARBAMAZEPINE; CIMETIDINE; CLONAZEPAM; CYCLOPHOSPHAMIDE; DIAZOXIDE; DICLOFENAC; DICLOXACILLIN; DIPHENHYDRAMINE; DIURETIC AGENT; DOXEPIN; ETHAMBUTOL; FELODIPINE; HALOPERIDOL; INDOMETACIN; LEVODOPA; LORATADINE; MELPHALAN; MERCAPTOPURINE; METHOTREXATE; PARACETAMOL; UNINDEXED DRUG;

CONFERENCE PAPER; DRUG EXCRETION; DRUG METABOLISM; DRUG SCREENING; DRUG STRUCTURE; DRUG TRANSFORMATION; DRUG URINE LEVEL; INTRAVENOUS DRUG ADMINISTRATION; MATHEMATICAL MODEL; PREDICTION; PRIORITY JOURNAL; REFERENCE VALUE; STRUCTURE ACTIVITY RELATION; URINARY EXCRETION; VALIDATION PROCESS;

EID: 0038407692     PISSN: 1611020X     EISSN: None     Source Type: Journal    
DOI: 10.1002/qsar.200390021     Document Type: Conference Paper

References (15)

1. Ohlstein, E. H., Ruffolo, R. R., and Elliott, J. D., Drug discovery in the next millennium, Ann. Rev. Pharmacol. Toxicol. 40, 177-191 (2000).
2. Rodrigues, A. D., Preclinical drug metabolism in the age of high-throughput screening, Pharm. Res. 14, 1504-1510 (1997).
3. Navia, M.A., and Chaturvedi, P.R., Design principles for orally bioavailable drugs, Drug Disc. Today 1, 179-189 (1996).
4. Gaviraghi, G., Barnaby, R. J., and Pellegatti, M., Pharmacokinetic challenges in lead optimisation, in: Testa, B., van de Waterbeemd, H., Folkers, G., Guy, R. (Eds.), Pharmacokinetic Optimisation in Drug Research, Wiley-VCH, Basel (Switzerland) 2001, pp. 1-14.
5. Kennedy, T., Managing the drug discovery/development interface, Drug Disc. Today 2, 436-444 (1997).
6. Ekins, S., Waller, C. L., Swaan, P. W., Cruciani, G., Wrighton, S. A., and Wikel, J. H., Progress in predicting ADME parameters in silico, J. Pharmacol. Toxicol. Meth. 44, 251-272 (2000).
7. Yoshida, F., and Topliss, J. G., QSAR model for drug human oral bioavailability, J. Med. Chem. 43, 2575-2585 (2000).
8. Andrews, C. W., Bennett, L., and Yu, L. Y., Predicting human bioavailability of a compound: development of a novel quantitative structure-bioavailability relationship, Pharm. Res. 17, 639-644 (2000).
9. Desousa, G., Florence, N., Valles, B., Coassolo, P., and Rahmani, R., Relationships between in vitro and in vivo biotransformation of drugs in humans and animals - pharmacological consequences, Cell. Biol. Toxicol. 11, 147-153 (1995).
10. Hardman, J. G., Goodman, A. G., and Limbird, L. E. (Eds.), Goodman and Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill, New York (USA) 1996, pp.1710-1792.
11. Scherrer, R. A., The treatment of ionizable compounds in quantitative structure-activity studies with special consideration of ion partitioning, ACS Symposium Series 255, 225-246 (1984).
12. Patel, H., and Cronin, M. T. D., A novel index for the description of molecular linearity, J. Chem. Inf. Comp. Sci. 41, 1228-1236 (2001).
13. Raevsky, O. A., Hydrogen bond strength estimation by means of the HYBOT program package, in: van de Waterbemd, Testa, B., Folkers, G. (Eds.), Computer-Assisted Lead Finding and Optimisation, Wiley-VCH, Basel (Switzerland) 1997, pp. 367-378.
14. Dearden, J. C., Partitioning and lipophilicity in quantitative structure-activity relationships, Environ. Health Perspect. 61, 203-228 (1985).
15. van de Waterbeemd, H., Smith, D.A., and Jones, B.C., Lipophilicity in PK design: methyl, ethyl, futile, J. Comput.Aided Mol. Design 15, 273-286 (2001).