title: Towards quantitative prediction of oral drug absorption.
abstract: Although several routes of administration can be considered for new drug entities, the oral route remains the most popular. To predict the in vivo performance of a drug after oral administration from in vitro data, it is essential that the factors limiting absorption can be modelled. Factors limiting oral drug absorption are typically slow and/or incomplete dissolution, formation of insoluble complexes and/or decomposition in the gastrointestinal lumen, poor net permeability and first-pass metabolism. Although many attempts have been made to make global forecasts of oral bioavailability based on a single parameter (ranging from the partition coefficient [logP] to the polar surface area), it is clear from the diversity of properties that can influence delivery of drugs via the oral route that such an approach can at best lead to a qualitative estimation. To predict in vivo performance in a more quantitative way, it is instead necessary to identify the extent to which each of the aforementioned factors can limit absorption, and then combine the information into a comprehensive model of the absorptive processes. Much progress has been made in the last 10 years on developing methods to pin down the extent to which each of the factors actually limits the absorption of a given compound and, concomitantly, physiological models have been evolved, which show promise in terms of being able to integrate the information generated about each of the individual limiting factors. This article attempts to summarize recent progress on the various fronts as a kind of 'progress report' towards quantitative prediction of oral drug absorption.
authors.affiliation: Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany. dressman@em.uni-frankfurt.de
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dressman
authors.forename: Kirstin
authors.initials: K
authors.lastname: Thelen
authors.forename: Ekarat
authors.initials: E
authors.lastname: Jantratid
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006801:Humans; D007408:Intestinal Absorption; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D010599:Pharmacokinetics; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations
references.citation: Pharm Res. 1998 Nov;15(11):1792-5
references.pmid: 9834005
references.citation: Pharm Res. 2002 Jun;19(6):868-74
references.pmid: 12134959
references.citation: Clin Pharmacol Ther. 2004 Oct;76(4):391
references.pmid: 15470340
references.citation: Annu Rev Nutr. 1996;16:383-415
references.pmid: 8839932
references.citation: Pharm Res. 2008 Jul;25(7):1663-76
references.pmid: 18404251
references.citation: Int J Pharm. 1999 Sep 20;186(2):119-25
references.pmid: 10486429
references.citation: Pharm Res. 1997 Apr;14(4):497-502
references.pmid: 9144738
references.citation: Drug Metab Dispos. 2007 Oct;35(10):1766-80
references.pmid: 17620347
references.citation: Pharm Res. 2006 Jan;23(1):165-76
references.pmid: 16308672
references.citation: Clin Pharmacokinet. 1984 May-Jun;9(3):211-21
references.pmid: 6329583
references.citation: Pharm Res. 1997 Jun;14(6):763-6
references.pmid: 9210194
references.citation: Clin Pharmacol Ther. 1985 Aug;38(2):205-11
references.pmid: 4017422
references.citation: J Clin Invest. 1987 Oct;80(4):1029-36
references.pmid: 3654968
references.citation: Eur J Clin Pharmacol. 1996;50(3):195-201
references.pmid: 8737759
references.citation: Expert Opin Drug Metab Toxicol. 2005 Aug;1(2):325-42
references.pmid: 16922646
references.citation: Biochem Pharmacol. 1989 May 1;38(9):1535-8
references.pmid: 2719725
references.citation: Expert Opin Drug Metab Toxicol. 2005 Jun;1(1):1-4
references.pmid: 16922647
references.citation: Adv Drug Deliv Rev. 2002 Mar 31;54(3):433-51
references.pmid: 11922957
references.citation: J Pharm Sci. 1998 May;87(5):626-33
references.pmid: 9572915
references.citation: Drug Discov Today Technol. 2005 Spring;2(1):125-32
references.pmid: 24981765
references.citation: Ann Emerg Med. 1986 Jul;15(7):843-6
references.pmid: 3729110
references.citation: Drug Metab Dispos. 2006 May;34(5):880-6
references.pmid: 16467132
references.citation: Drug Discov Today. 2002 Jun 1;7(11):S83-8
references.pmid: 12047885
references.citation: Gastroenterology. 1989 Mar;96(3):736-49
references.pmid: 2914637
references.citation: J Med Chem. 1998 Dec 3;41(25):4939-49
references.pmid: 9836611
references.citation: FASEB J. 1992 Jan 6;6(2):745-8
references.pmid: 1537465
references.citation: Am J Dig Dis. 1966 Jul;11(7):503-21
references.pmid: 5937767
references.citation: Eur J Clin Pharmacol. 1981 Mar;19(4):271-8
references.pmid: 6116606
references.citation: Pharmacol Rev. 1999 Jun;51(2):135-58
references.pmid: 10353984
references.citation: Eur J Pharm Biopharm. 2005 Aug;60(3):413-7
references.pmid: 15893920
references.citation: Pharm Res. 2003 Dec;20(12):1961-9
references.pmid: 14725360
references.citation: Eur J Pharm Sci. 2002 Oct;17(1-2):51-61
references.pmid: 12356420
references.citation: Int J Pharm. 2005 Apr 11;293(1-2):183-92
references.pmid: 15778056
references.citation: J Pharm Sci. 1986 Feb;75(2):109-16
references.pmid: 3958917
references.citation: J Biomol Screen. 2001 Jun;6(3):189-96
references.pmid: 11689115
references.citation: Pharm Res. 2006 Jun;23(6):1144-56
references.pmid: 16715363
references.citation: Drug Metab Dispos. 1996 Oct;24(10):1121-3
references.pmid: 8894514
references.citation: J Med Chem. 2004 Jul 29;47(16):4022-31
references.pmid: 15267240
references.citation: Curr Drug Metab. 2007 Oct;8(7):676-84
references.pmid: 17979655
references.citation: Clin Pharmacokinet. 2006;45(12):1213-26
references.pmid: 17112297
references.citation: J Pharm Pharmacol. 2007 Oct;59(10):1335-43
references.pmid: 17910807
references.citation: Pharm Res. 1998 Jan;15(1):11-22
references.pmid: 9487541
references.citation: Eur J Pharm Sci. 2000 Oct;11 Suppl 2:S73-80
references.pmid: 11033429
references.citation: J Pharmacokinet Pharmacodyn. 2007 Jun;34(3):401-31
references.pmid: 17431751
references.citation: J Med Chem. 2001 Mar 15;44(6):923-30
references.pmid: 11300874
references.citation: Int J Pharm. 2004 Apr 15;274(1-2):221-32
references.pmid: 15072798
references.citation: Clin Pharmacokinet. 2006;45(4):385-99
references.pmid: 16584285
references.citation: J Pharmacol Exp Ther. 1997 Dec;283(3):1552-62
references.pmid: 9400033
references.citation: Drug Metab Dispos. 1999 Feb;27(2):180-7
references.pmid: 9929500
references.citation: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):27-43
references.pmid: 11259831
references.citation: J Pharm Sci. 1968 Aug;57(8):1322-6
references.pmid: 5677333
references.citation: Eur J Pharm Sci. 2001 Sep;14(2):115-22
references.pmid: 11500257
references.citation: Kidney Int. 2003 Mar;63(3):1072-8
references.pmid: 12631090
references.citation: Arch Biochem Biophys. 1998 May 1;353(1):16-28
references.pmid: 9578596
references.citation: J Pharmacol Exp Ther. 1994 Jul;270(1):414-23
references.pmid: 8035341
references.citation: Drug Metab Dispos. 1999 Jul;27(7):804-9
references.pmid: 10383924
references.citation: Pharm Res. 2007 Jul;24(7):1275-82
references.pmid: 17373575
references.citation: Eur J Clin Pharmacol. 1977 Dec 2;12(4):297-303
references.pmid: 590315
references.citation: Eur J Pharm Sci. 2001 Oct;14(3):237-44
references.pmid: 11576829
references.citation: J Pharmacol Exp Ther. 2006 Sep;318(3):1220-9
references.pmid: 16763093
references.citation: Am J Physiol. 1999 Mar;276(3):G789-94
references.pmid: 10070058
references.citation: J Pharm Sci. 2007 Mar;96(3):522-31
references.pmid: 17117431
references.citation: Clin Pharmacol Ther. 2001 Sep;70(3):217-27
references.pmid: 11557909
references.citation: J Pharm Sci. 1998 Apr;87(4):403-10
references.pmid: 9548891
references.citation: J Biol Chem. 1986 Apr 15;261(11):5051-60
references.pmid: 3514607
references.citation: Pharm Res. 1995 May;12(5):693-9
references.pmid: 7479555
references.citation: Pharm Res. 1996 Jan;13(1):120-3
references.pmid: 8668660
references.citation: Expert Opin Drug Metab Toxicol. 2005 Jun;1(1):159-68
references.pmid: 16922658
references.citation: Adv Drug Deliv Rev. 2008 Mar 17;60(6):717-33
references.pmid: 18199522
references.citation: J Med Chem. 1998 Mar 26;41(7):1007-10
references.pmid: 9544199
references.citation: Eur J Pharm Sci. 2006 Jan;27(1):91-9
references.pmid: 16219449
references.citation: J Pharm Sci. 2007 Nov;96(11):2893-909
references.pmid: 17803196
references.citation: Clin Pharmacokinet. 1993 Jun;24(6):472-95
references.pmid: 8513650
references.citation: Adv Drug Deliv Rev. 2001 Oct 1;50 Suppl 1:S41-67
references.pmid: 11576695
references.citation: Eur J Med Chem. 2002 May;37(5):399-407
references.pmid: 12008054
references.citation: Lancet. 1991 Dec 14;338(8781):1488-90
references.pmid: 1683920
references.citation: Clin Pharmacol Ther. 1984 Jun;35(6):742-9
references.pmid: 6734025
references.citation: Clin Pharmacol Ther. 1996 Jul;60(1):14-24
references.pmid: 8689807
references.citation: Pharm Res. 1996 Feb;13(2):216-21
references.pmid: 8932439
references.citation: J Control Release. 2000 Mar 1;65(1-2):55-62
references.pmid: 10699270