A 'rule of unity' for human intestinal absorption

S. H. Yalkowsky, J. L.H. Johnson, T. Sanghvi, S. G. Machatha

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


The ability to predict the passive intestinal absorption of organic compounds can be a valuable tool in drug design. Although Lipinski's 'rule of 5' is commonly used for this purpose, it does not routinely give reliable results. An alternative 'rule of unity' is proposed to predict the absorption efficiency of orally administered drugs that are passively transported. The rule of unity based upon the theoretical principals that govern passive transport. The 'rule of 5' and the 'rule of unity' are compared using experimentally determined passive human intestinal absorption data for 155 drugs. Absorption values which are >50% of the dose are classified as well absorbed and absorption values which are 50% of the dose are classified as classified as poorly absorbed. Comparison of the two models using a receiver operating characteristic (ROC) plot and McNemar's test reveal striking differences in absorption predictability. The 'rule of 5' gives twice as many false predictions than the 'rule of unity.'

Original languageEnglish (US)
Pages (from-to)2475-2481
Number of pages7
JournalPharmaceutical Research
Issue number10
StatePublished - Oct 2006


  • "Rule of 5"
  • "Rule of unity"
  • Absorption
  • Passive transportation
  • Solubility

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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