Drug Absorption Principles

  • Xianhua Cao
  • Lawrence Yu
  • Duxin Sun

Pharmacokinetics describes drug absorption, distribution, metabolism, and excretion processes. Absorption is the rate and extent at which drugs reach the systemic circulation from the site of administration. Distribution of a drug includes all the processes that are involved from the time when the drug reaches the circulation to the time when it (or a metabolite of the drug) leaves the body. Metabolism involves all the biochemical processes that result in a chemical change to the drug compound including both the metabolism in the gut wall, the liver, and blood circulation. Excretion is the process in which the drug is eliminated from the systemic circulation into bile, urine, feces, sweat, and air (Allen, 1982). The reader is referred to authoritative texts in this area for a detailed review.


Drug Absorption Passive Diffusion Drug Permeability Paracellular Transport Release Dosage Form 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allen L, MacKichan J and Ritschel WA (1982) Manual of symbols, equations & definitions in pharmacokinetics. J Clin Pharmacol 22:1S-23S.CrossRefGoogle Scholar
  2. Amidon GL, Sinko PJ and Fleisher D (1988) Estimating human oral fraction dose absorbed: a correlation using rat intestinal membrane permeability for passive and carrier-mediated compounds. Pharm Res 5:651-654.CrossRefPubMedGoogle Scholar
  3. Amidon GL, Lennernas H, Shah VP and Crison JR (1995) A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 12:413-420.CrossRefPubMedGoogle Scholar
  4. Anderle P, Huang Y and Sadee W (2004) Intestinal membrane transport of drugs and nutri-ents: genomics of membrane transporters using expression microarrays. Eur J Pharm Sci 21:17-24.CrossRefPubMedGoogle Scholar
  5. Anderson JR and Pitman IH (1980) Solubility and dissolution rate studies of ergotamine tartrate. J Pharm Sci 69:832-835.CrossRefPubMedGoogle Scholar
  6. Atkinson AJ Jr (2001) Drug absorption and bioavailability. Princ Clin Pharmacol 31-41.Google Scholar
  7. Badawy SIF, Gray DB, Zhao F, Sun D, Schuster AE and Hussain MA (2006) Formulation of solid dosage forms to overcome gastric pH interaction of the factor Xa inhibitor, BMS- 561389. Pharm Res 23:989-996.CrossRefPubMedGoogle Scholar
  8. Burton PS, Goodwin JT, Vidmar TJ and Amore BM (2002) Predicting drug absorption: how nature made it a difficult problem. J Pharmacol Exp Ther 303:889-895.CrossRefPubMedGoogle Scholar
  9. Cainelli SR, Chui A, McClure JD Jr and Hunter FR (1974) Facilitated diffusion in erythrocytes of mammals. Comp Biochem Physiol A 48:815-825.CrossRefPubMedGoogle Scholar
  10. Cao X, Yu LX, Barbaciru C, Landowski CP, Shin HC, Gibbs S, Miller HA, Amidon GL and Sun D (2005) Permeability dominates in vivo intestinal absorption of P-gp substrate with high solubility and high permeability. Mol Pharm 2:329-340.CrossRefPubMedGoogle Scholar
  11. Cao X, Gibbs ST, Fang L, Miller HA, Landowski CP, Shin HC, Lennernas H, Zhong Y, Amidon GL, Yu LX and Sun D (2006) Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model. Pharm Res 23:1675-1686.CrossRefPubMedGoogle Scholar
  12. Chidambaram N and Burgess DJ (2000) Mathematical modeling of surface-active and non-surface-active drug transport in emulsion systems. AAPS Pharm Sci 2:E31.Google Scholar
  13. Chiou WL (2001) The rate and extent of oral bioavailability versus the rate and extent of oral absorption: clarification and recommendation of terminology. J Pharmacokinet Pharmacodyn 28:3-6.CrossRefPubMedGoogle Scholar
  14. Chiou WL and Barve A (1998) Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats. Pharm Res 15:1792-1795.CrossRefPubMedGoogle Scholar
  15. Chiou WL and Buehler PW (2002) Comparison of oral absorption and bioavailability of drugs between monkey and human. Pharm Res 19:868-874.CrossRefPubMedGoogle Scholar
  16. Chong S, Dando SA, Soucek KM and Morrison RA (1996) In vitro permeability through caco-2 cells is not quantitatively predictive of in vivo absorption for peptide-like drugs absorbed via the dipeptide transporter system. Pharm Res 13:120-123.CrossRefPubMedGoogle Scholar
  17. Curatolo W (1987) The lipoidal permeability barriers of the skin and alimentary tract. Pharm Res 4:271-277.CrossRefPubMedGoogle Scholar
  18. Daugherty AL and Mrsny RJ (1999) Transcellular uptake mechanisms of the intestinal epithelial barrier Part one. Pharm Sci Technol Today 4:144-151.CrossRefPubMedGoogle Scholar
  19. Dressman JB, Amidon GL, Reppas C and Shah VP (1998) Dissolution testing as a prognos-tic tool for oral drug absorption: immediate release dosage forms. Pharm Res 15:11-22.CrossRefPubMedGoogle Scholar
  20. Fagerholm U, Johansson M and Lennernas H (1996) Comparison between permeability coefficients in rat and human jejunum. Pharm Res 13:1336-1342.CrossRefPubMedGoogle Scholar
  21. Feher JJ (1983) Facilitated calcium diffusion by intestinal calcium-binding protein. Am J Physiol 244:C303-307.PubMedGoogle Scholar
  22. Fleisher D, Lippert CL, Sheth N, Reppas C and Wlodyga J (1990) Nutrient effects on intestinal drug absorption. J Control Release 11:41-49.CrossRefGoogle Scholar
  23. Frenning G and Stromme M (2003) Drug release modeled by dissolution, diffusion, and immobilization. Int J Pharm 250:137-145.CrossRefPubMedGoogle Scholar
  24. Hansen JE, Weisbart RH and Nishimura RN (2005) Antibody mediated transduction of therapeutic proteins into living cells. Scientific World Journal 5:782-788.PubMedGoogle Scholar
  25. Higuchi WI and Ho NFH (1988) Membrane transfer of drugs. Int J Pharm 2:10-15.Google Scholar
  26. Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, Toguchi H, Liversidge GG, Higaki K and Kimura T (2006) Effect of particle size reduction on dissolution and oral absorption of a poorly water-soluble drug, cilostazol, in beagle dogs. J Control Release 111:56-64.CrossRefPubMedGoogle Scholar
  27. Kwan KC (1997) Oral bioavailability and first-pass effects. Drug Metab Dispos 25:1329-1336.PubMedGoogle Scholar
  28. Lennernas H (1998) Human intestinal permeability. J Pharm Sci 87:403-410.CrossRefPubMedGoogle Scholar
  29. Lennernas H, Nylander S and Ungell AL (1997) Jejunal permeability: a comparison between the Using chamber technique and the single-pass perfusion in humans. Pharm Res 14:667-671.CrossRefPubMedGoogle Scholar
  30. Liang XJ, Mukherjee S, Shen DW, Maxfield FR and Gottesman MM (2006) Endocytic recycling compartments altered in cisplatin-resistant cancer cells. Cancer Res 66: 2346-2353.CrossRefPubMedGoogle Scholar
  31. Narawane L and Lee VHL (1994) Absorption barriers. Drug Target Deliv 3:1-66.Google Scholar
  32. Oh DM, Curl RL and Amidon GL (1993) Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: a mathematical model. Pharm Res 10:264-270.CrossRefPubMedGoogle Scholar
  33. Oh DM, Han HK and Amidon GL (1999) Drug transport and targeting. Intestinal transport. Pharm Biotechnol 12:59-88.CrossRefPubMedGoogle Scholar
  34. Pade V and Stavchansky S (1998) Link between drug absorption solubility and permeability measurements in Caco-2 cells. J Pharm Sci 87:1604-1607.CrossRefPubMedGoogle Scholar
  35. Rouge N, Buri P and Doelker E (1996) Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery. Int J Pharm 136:117-139.CrossRefGoogle Scholar
  36. Schreiner T, Schaefer UF and Loth H (2005) Immediate drug release from solid oral dosage forms. J Pharm Sci 94:120-133.CrossRefPubMedGoogle Scholar
  37. Shin H-C, Landowski CP, Sun D, Vig BS, Kim I, Mittal S, Lane M, Rosania G, Drach JC and Amidon GL (2003) Functional expression and characterization of a sodium-dependent nucleoside transporter hCNT2 cloned from human duodenum. Biochem Bio-phys Res Commun 307:696-703.CrossRefGoogle Scholar
  38. Sun D, Lennernas H, Welage LS, Barnett JL, Landowski CP, Foster D, Fleisher D, Lee KD and Amidon GL (2002) Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs. Pharm Res 19:1400-1416.CrossRefPubMedGoogle Scholar
  39. Sun D, Yu LX, Hussain MA, Wall DA, Smith RL and Amidon GL (2004) 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 7:75-85.PubMedGoogle Scholar
  40. Toutain PL and Bousquet-Melou A (2004) Bioavailability and its assessment. J Vet Phar-macol Ther 27:455-466.CrossRefGoogle Scholar
  41. Trischitta F, Denaro MG, Faggio C and Lionetto MG (2001) Ca++ regulation of paracellular permeability in the middle intestine of the eel, Anguilla anguilla. J Comp Physiol [B] 171:85-90.Google Scholar
  42. Ungell AL, Nylander S, Bergstrand S, Sjoeberg A and Lennernaes H (1998) Membrane transport of drugs in different regions of the intestinal tract of the Rat. J Pharm Sci 87:360-366.CrossRefPubMedGoogle Scholar
  43. Watanabe E, Takahashi M and Hayashi M (2004) A possibility to predict the absorbability of poorly water-soluble drugs in humans based on rat intestinal permeability assessed by an in vitro chamber method. Eur J Pharm Biopharm 58:659-665.CrossRefPubMedGoogle Scholar
  44. Yamashita S, Furubayashi T, Kataoka M, Sakane T, Sezaki H and Tokuda H (2000) Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells. Eur J Pharm Sci 10:195-204.CrossRefPubMedGoogle Scholar
  45. Yee S (1997) In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man-fact or myth. Pharm Res 14:763-766.CrossRefPubMedGoogle Scholar
  46. Yoon KA and Burgess DJ (1998) Mathematical modelling of drug transport in emulsion systems. J Pharm Pharmacol 50:601-610.PubMedGoogle Scholar
  47. Yu LX and Amidon GL (1999) A compartmental absorption and transit model for estimating oral drug absorption. Int J Pharm 186:119-125.CrossRefPubMedGoogle Scholar
  48. Yu LX, Lipka E, Crison JR and Amidon GL (1996) Transport approaches to the biopharmaceutical design of oral drug delivery systems: prediction of intestinal absorption. Adv Drug Deliv Rev 19:359-376.CrossRefPubMedGoogle Scholar
  49. Zhao YH, Abraham MH, Le J, Hersey A, Luscombe CN, Beck G, Sherborne B and Cooper I (2003) Evaluation of rat intestinal absorption data and correlation with human intestinal absorption. Eur J Med Chem 38:233-243.CrossRefPubMedGoogle Scholar
  50. Zhou R, Moench P, Heran C, Lu X, Mathias N, Faria Teresa N, Wall Doris A, Hussain Munir A, Smith RL and Sun D (2005) pH-dependent dissolution in vitro and absorption in vivo of weakly basic drugs: development of a canine model. Pharm Res 22:188-192.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Xianhua Cao
    • 1
  • Lawrence Yu
    • 2
  • Duxin Sun
    • 1
  1. 1.College of PharmacyThe Ohio State UniversityColumbusUSA
  2. 2.Food and Drug AdministrationCenter for Drug Evaluation & ResearchRockvilleUSA

Personalised recommendations