Software & Consulting For The Pharmaceutical Scientist


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The maximum absorbable dose (MAD) calculation was conceptualized by Kevin C. Johnson, Ph.D. while working for Pfizer during the late '80s and first published by Kevin C. Johnson and Archie C. Swindell in a paper entitled "Guidance in the Setting of Drug Particle Size Specification to Minimize Variability in Absorption", Pharmaceutical Research, Vol. 13, No. 12, 1996, pages 1795-1798.  Since that time, the MAD calculation has been frequently cited in both the printed literature and on the world wide web, and is used as a standard metric by several pharmaceutical companies for assessing the challenges in developing potential drug candidates.

Citations:

1. Seshadri Neervannan. Strategies to Impact Solubility and Dissolution Rate During Drug Lead Optimization: Salt Selection and Prodrug Design Approaches. American Pharmaceutical Review, 2004 Vol. 7, Issue 5, pages 108-113.

2. David R. Friend. Drug Delivery to the Small Intestine. Current Gastroenterology Reports. 2004 6:371-376.

3. D Sun, LX Yu, MA Hussain, DA Wall, RL Smith, GL Amidon.  In vitro testing of drug absorption for drug 'developability' assessment:  forming an interface between in vitro preclinical data and clinical outcome. Curr Opin Drug Discov Devel. 2004 7(1):75-85.

4. AF Hadfield et al. United States Patent Application 20040044241 (3/4/04).

5. LF Huang, WQ Tong. Impact of solid state properties on developability assessment of drug candidates.  Advanced Drug Delivery Reviews. 2004 56:321-334.

6. N. Rasenack, BW Muller.  Micron-size drug particles: Common and novel micronization techniques. Pharmaceutical Development and Technology. 2004 9(1):1-13.

7. S Tolle-Sander, A Grill, H Joshi, et al. Characterization of dexloxiglumide in vitro biopharmaceutical properties and active transport. J Pharm Sci. 2003 92(10):1968-1980.

8. T Sanghvi, N Ni, M Mayersohn, et al. Predicting passive intestinal absorption using a single parameter. QSAR Comb Sci. 2003 22(2):247-257.

9. AR Hilgers, DP Smith, JJ Biermacher, JS Day, JL Jensen, SM Sims, WJ Adams, JM Friis, J Palandra, JD Hosley, EM Shobe, PS Burton. Predicting Oral Absorption of Drugs: A Case Study with a Novel Class of Antimicrobial Agents. Pharm Res. 2003 20(8):1149-1155.

10. EF "Gene" Fiese. General Pharmaceutics-The new physical pharmacy. J Pharm Sci. 2003 92(7):1331-1342.

11. VK Gombar, IS Silver, ZY Zhao. Role of ADME characteristics in drug discovery and their in silico evaluation: In silico screening of chemicals for their metabolic stability. Curr Top Med Chem. 2003 3(11):1205-1225.

12. CAS Bergstrom, M Strafford, L Lazorova, et al. Absorption classification of oral drugs based on molecular surface properties. J Med Chem. 2003 46(4):558-570.

13. Helena Engman. Intestinal Barriers to Oral Drug Absorption. Cytochrome P450 and ABC-Transport Proteins. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 296. ACTA UNIVERSITATIS UPSALIENSIS. UPPSALA 2003

14. Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability, edited by H. vande Waterbeemd, H. Lennernas and P. Artursson, Volume 18 of Methods and Principles in Medicinal Chemistry, Copyright 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

15. Absorption and drug development: solubility, permeability, and charge state, Alex Avdeef, Copyright 2003 by John Wiley & Sons, Inc. Hoboken, New Jersey.

16. PS Burton, JT Goodwin, TJ Vidmar, et al. Predicting drug absorption: How nature made it a difficult problem. J Pharmacol Exp Ther. 2002 303(3):889-895.

17. P Stenberg, CAS Bergstrom, K Luthman, et al. Theoretical predictions of drug absorption in drug discovery and development. Clin Pharmacokinet. 2002 41(11):877-899.

18. WJ Egan, G Lauri. Prediction of Intestinal Permeability. Adv Drug Deliver Rev. 2002 54:273-289.

19. DA Smith, H van de Waterbeemd, DK Walker (ed.). in Pharmacokinetics and Metabolism in Drug Design. Copyright 2001 Wiley-VCH Verlag GmbH.

20. A Ohm. Interation of Bay t3839 Coprecipitates with Insoluble Excipients. Eur J Pharm Biopharm. 2000 49:183-189.

21. BH Stewart, Y Wang, N Surendran. Ex Vivo Approaches to Predicting Oral Pharmacokinetics in Humans. Annu Rep Med Chem. 2000 54:299-307.

22. JR Crison. Biopharmaceutical Aspects of Water-Insoluble Drugs for Oral Drug Delivery in Water-Insoluble Drug Formulation. Rong Liu (ed.). Copyright 2000 Interpharm Press. Englewood, CO.

23. JF Blake. Chemoinformatics-predicting the physicochemical properties of "drug-like" molecules. Curr Opin Biotech. 2000 11(1):104-7.

24. H Boxenbaum. Absorption Potential and Its Variants. Pharm Res. 1999 16(12):1893.

25. F Lombardo, SM Winter, L Tremaine, JA Lowe. The Anxieties of Drug Discovery and Development in Integration of Pharmaceutical Discovery and Development: Case Studies. R Borchardt, et al. (ed.). copyright 1998 Plenum Press, New York.

26. W Curatolo. Physical chemical properties of oral drug candidates in the discovery and exploratory development setting. PSTT. 1998 1(9):387-393.

27. RLA De Vrueh, PL Smith, CP Lee. Transport of L-valine-acyclovir via the oligopeptide transporter in the human intestinal cell line. J Pharmacol Exp Ther. 1998 286(3):1166-1170.

Per E.Nielsen "Going MAD Without a Rat - Versatility of the PAMPA Permeability Assay"

Patrizia Crivori, Ph.D. "Approaches for Predicting Intestinal Absorption of Drug Candidates"

Dr. Konstantin Tsinman "MAD Analysis Using HT Solubility and Rat in situ/Caco-2 Data Modelled with PAMPA"

Dr. Konstantin Tsinman "Maximum Absorbable Dose - MAD analysis using permeability and solubility"

Anand Sistla, Ph.D. "Importance and MTS Screening of Physiochemical Parameters in Drug Discovery"

Alex Avdeef, Ph.D. "Second Generation PAMPA for MAD (Maximum Absorbable Dose) Analysis"

E. F. "Gene" Fiese, Ph.D. "Assessing Rate Limiting Factors"

Kevin C. Johnson, Ph.D. "Prediction Models For Drug Absorption"

Dr. Hans Briem "Lead Optimization: From Leads to Developmental Candidates"

ADMETRx

In silico tools to predict absorption

AAPS Workshop on Optimization of Drug-Like Properties During Lead Optimization:

    Philip S. Burton, Ph.D. "Computational Methods for Physicochemical  Property-Based Optimization of Drug Discovery Leads"

    Li Di, Ph.D. "Application of Physicochemical Data to Support Lead Optimization by Discovery Teams"

    Brian R. Rohrs, Ph.D. "Biopharmaceutic Modeling and the Role of Dose and Formulation on Oral Exposure"    

    Gail L Strong, Ph.D. "The Importance of Solubility and Salt Selection in Obtaining In Vivo Exposure"

B. Faller "Enhancing Knowledge through Combination of in-silico and in-vitro ADME Profiling Assays"

Alex Avdeef, Ph.D., "The "MAD" Drug Absorption Model:  Based on the Combination of Permeability, Solubility, and Charge State"

Edmund Hoppe, "From Chemicals to Drugs"

Dr. Bruno Galli, "Selection of Candidates and their Pharmaceutical Developability"

Physicochemical properties required for an optimal systemic availability of drugs in relation to the route of administration


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