Intestinal permeability and its relevance for absorption and elimination - PubMed

Affiliations

• PMID: 17968735
• DOI: 10.1080/00498250701704819

Review

Intestinal permeability and its relevance for absorption and elimination

H Lennernäs. Xenobiotica. 2007 Oct-Nov.

Abstract

Human jejunal permeability (P(eff)) is determined in the intestinal region with the highest expression of carrier proteins and largest surface area. Intestinal P(eff) are often based on multiple parallel transport processes. Site-specific jejunal P(eff) cannot reflect the permeability along the intestinal tract, but they are useful for approximating the fraction oral dose absorbed. It seems like drugs with a jejunal P(eff) > 1.5 x 10(-4) cm s(-1) will be completely absorbed no matter which transport mechanism(s) are utilized. Many drugs that are significantly effluxed in vitro have a rapid and complete intestinal absorption (i.e. >85%) mediated by passive transcellular diffusion. The determined jejunal P(eff) for drugs transported mainly by absorptive carriers (such as peptide and amino acid transporters) will accurately predict the fraction of the dose absorbed as a consequence of the regional expression. The data also show that: (1) the human intestinal epithelium has a large resistance towards large and hydrophilic compounds; and (2) the paracellular route has a low contribution for compounds larger than approximately molecular weight 200. There is a need for more exploratory in vivo studies to clarify drug absorption and first-pass extraction along the intestine. One is encouraged to develop in vivo perfusion techniques for more distal parts of the gastrointestinal tract in humans. This would stimulate the development of more relevant and complex in vitro absorption models and form the basis for an accurate physiologically based pharmacokinetic modelling of oral drug absorption.

Similar articles

• Frog intestinal sac as an in vitro method for the assessment of intestinal permeability in humans: Application to carrier transported drugs.

  Franco M, Lopedota A, Trapani A, Cutrignelli A, Meleleo D, Micelli S, Trapani G. Franco M, et al. Int J Pharm. 2008 Mar 20;352(1-2):182-8. doi: 10.1016/j.ijpharm.2007.10.027. Epub 2007 Dec 11. Int J Pharm. 2008. PMID: 18055143

• Theoretical investigation of passive intestinal membrane permeability using Monte Carlo method to generate drug-like molecule population.

  Sugano K. Sugano K. Int J Pharm. 2009 May 21;373(1-2):55-61. doi: 10.1016/j.ijpharm.2009.02.002. Epub 2009 Feb 12. Int J Pharm. 2009. PMID: 19429288

• Human intestinal permeability.

  Lennernäs H. Lennernäs H. J Pharm Sci. 1998 Apr;87(4):403-10. doi: 10.1021/js970332a. J Pharm Sci. 1998. PMID: 9548891 Review.

• Characterization of jejunal absorption and apical efflux of ropivacaine, lidocaine and bupivacaine in the rat using in situ and in vitro absorption models.

  Berggren S, Hoogstraate J, Fagerholm U, Lennernäs H. Berggren S, et al. Eur J Pharm Sci. 2004 Mar;21(4):553-60. doi: 10.1016/j.ejps.2003.12.004. Eur J Pharm Sci. 2004. PMID: 14998587

• Regional intestinal drug permeation: biopharmaceutics and drug development.

  Lennernäs H. Lennernäs H. Eur J Pharm Sci. 2014 Jun 16;57:333-41. doi: 10.1016/j.ejps.2013.08.025. Epub 2013 Aug 27. Eur J Pharm Sci. 2014. PMID: 23988845 Review.

Cited by

• Physiologically Based Biopharmaceutics Modeling of Regional and Colon Absorption in Dogs.

  Eckernäs E, Tannergren C. Eckernäs E, et al. Mol Pharm. 2021 Apr 5;18(4):1699-1710. doi: 10.1021/acs.molpharmaceut.0c01201. Epub 2021 Mar 15. Mol Pharm. 2021. PMID: 33720733 Free PMC article.

• Levothyroxine: Conventional and Novel Drug Delivery Formulations.

  Liu H, Li W, Zhang W, Sun S, Chen C. Liu H, et al. Endocr Rev. 2023 May 8;44(3):393-416. doi: 10.1210/endrev/bnac030. Endocr Rev. 2023. PMID: 36412275 Free PMC article. Review.

• An in vitro toolbox to accelerate anti-malarial drug discovery and development.

  Charman SA, Andreu A, Barker H, Blundell S, Campbell A, Campbell M, Chen G, Chiu FCK, Crighton E, Katneni K, Morizzi J, Patil R, Pham T, Ryan E, Saunders J, Shackleford DM, White KL, Almond L, Dickins M, Smith DA, Moehrle JJ, Burrows JN, Abla N. Charman SA, et al. Malar J. 2020 Jan 2;19(1):1. doi: 10.1186/s12936-019-3075-5. Malar J. 2020. PMID: 31898492 Free PMC article.

• Bioequivalence of oral products and the biopharmaceutics classification system: science, regulation, and public policy.

  Amidon KS, Langguth P, Lennernäs H, Yu L, Amidon GL. Amidon KS, et al. Clin Pharmacol Ther. 2011 Sep;90(3):467-70. doi: 10.1038/clpt.2011.109. Epub 2011 Jul 20. Clin Pharmacol Ther. 2011. PMID: 21775984 Free PMC article. Review.

• Oral antibiotic therapy for acne vulgaris: pharmacokinetic and pharmacodynamic perspectives.

  Leyden JJ, Del Rosso JQ. Leyden JJ, et al. J Clin Aesthet Dermatol. 2011 Feb;4(2):40-7. J Clin Aesthet Dermatol. 2011. PMID: 21386956 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon

• Other Literature Sources

  • The Lens - Patent Citations Database