Towards quantitative prediction of oral drug absorption.
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.
Dressman
Jennifer B
JB
Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany. dressman@em.uni-frankfurt.de
Thelen
Kirstin
K
Jantratid
Ekarat
E
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
D004364:Pharmaceutical Preparations
Pharm Res. 1998 Nov;15(11):1792-5
9834005
Pharm Res. 2002 Jun;19(6):868-74
12134959
Clin Pharmacol Ther. 2004 Oct;76(4):391
15470340
Annu Rev Nutr. 1996;16:383-415
8839932
Pharm Res. 2008 Jul;25(7):1663-76
18404251
Int J Pharm. 1999 Sep 20;186(2):119-25
10486429
Pharm Res. 1997 Apr;14(4):497-502
9144738
Drug Metab Dispos. 2007 Oct;35(10):1766-80
17620347
Pharm Res. 2006 Jan;23(1):165-76
16308672
Clin Pharmacokinet. 1984 May-Jun;9(3):211-21
6329583
Pharm Res. 1997 Jun;14(6):763-6
9210194
Clin Pharmacol Ther. 1985 Aug;38(2):205-11
4017422
J Clin Invest. 1987 Oct;80(4):1029-36
3654968
Eur J Clin Pharmacol. 1996;50(3):195-201
8737759
Expert Opin Drug Metab Toxicol. 2005 Aug;1(2):325-42
16922646
Biochem Pharmacol. 1989 May 1;38(9):1535-8
2719725
Expert Opin Drug Metab Toxicol. 2005 Jun;1(1):1-4
16922647
Adv Drug Deliv Rev. 2002 Mar 31;54(3):433-51
11922957
J Pharm Sci. 1998 May;87(5):626-33
9572915
Drug Discov Today Technol. 2005 Spring;2(1):125-32
24981765
Ann Emerg Med. 1986 Jul;15(7):843-6
3729110
Drug Metab Dispos. 2006 May;34(5):880-6
16467132
Drug Discov Today. 2002 Jun 1;7(11):S83-8
12047885
Gastroenterology. 1989 Mar;96(3):736-49
2914637
J Med Chem. 1998 Dec 3;41(25):4939-49
9836611
FASEB J. 1992 Jan 6;6(2):745-8
1537465
Am J Dig Dis. 1966 Jul;11(7):503-21
5937767
Eur J Clin Pharmacol. 1981 Mar;19(4):271-8
6116606
Pharmacol Rev. 1999 Jun;51(2):135-58
10353984
Eur J Pharm Biopharm. 2005 Aug;60(3):413-7
15893920
Pharm Res. 2003 Dec;20(12):1961-9
14725360
Eur J Pharm Sci. 2002 Oct;17(1-2):51-61
12356420
Int J Pharm. 2005 Apr 11;293(1-2):183-92
15778056
J Pharm Sci. 1986 Feb;75(2):109-16
3958917
J Biomol Screen. 2001 Jun;6(3):189-96
11689115
Pharm Res. 2006 Jun;23(6):1144-56
16715363
Drug Metab Dispos. 1996 Oct;24(10):1121-3
8894514
J Med Chem. 2004 Jul 29;47(16):4022-31
15267240
Curr Drug Metab. 2007 Oct;8(7):676-84
17979655
Clin Pharmacokinet. 2006;45(12):1213-26
17112297
J Pharm Pharmacol. 2007 Oct;59(10):1335-43
17910807
Pharm Res. 1998 Jan;15(1):11-22
9487541
Eur J Pharm Sci. 2000 Oct;11 Suppl 2:S73-80
11033429
J Pharmacokinet Pharmacodyn. 2007 Jun;34(3):401-31
17431751
J Med Chem. 2001 Mar 15;44(6):923-30
11300874
Int J Pharm. 2004 Apr 15;274(1-2):221-32
15072798
Clin Pharmacokinet. 2006;45(4):385-99
16584285
J Pharmacol Exp Ther. 1997 Dec;283(3):1552-62
9400033
Drug Metab Dispos. 1999 Feb;27(2):180-7
9929500
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):27-43
11259831
J Pharm Sci. 1968 Aug;57(8):1322-6
5677333
Eur J Pharm Sci. 2001 Sep;14(2):115-22
11500257
Kidney Int. 2003 Mar;63(3):1072-8
12631090
Arch Biochem Biophys. 1998 May 1;353(1):16-28
9578596
J Pharmacol Exp Ther. 1994 Jul;270(1):414-23
8035341
Drug Metab Dispos. 1999 Jul;27(7):804-9
10383924
Pharm Res. 2007 Jul;24(7):1275-82
17373575
Eur J Clin Pharmacol. 1977 Dec 2;12(4):297-303
590315
Eur J Pharm Sci. 2001 Oct;14(3):237-44
11576829
J Pharmacol Exp Ther. 2006 Sep;318(3):1220-9
16763093
Am J Physiol. 1999 Mar;276(3):G789-94
10070058
J Pharm Sci. 2007 Mar;96(3):522-31
17117431
Clin Pharmacol Ther. 2001 Sep;70(3):217-27
11557909
J Pharm Sci. 1998 Apr;87(4):403-10
9548891
J Biol Chem. 1986 Apr 15;261(11):5051-60
3514607
Pharm Res. 1995 May;12(5):693-9
7479555
Pharm Res. 1996 Jan;13(1):120-3
8668660
Expert Opin Drug Metab Toxicol. 2005 Jun;1(1):159-68
16922658
Adv Drug Deliv Rev. 2008 Mar 17;60(6):717-33
18199522
J Med Chem. 1998 Mar 26;41(7):1007-10
9544199
Eur J Pharm Sci. 2006 Jan;27(1):91-9
16219449
J Pharm Sci. 2007 Nov;96(11):2893-909
17803196
Clin Pharmacokinet. 1993 Jun;24(6):472-95
8513650
Adv Drug Deliv Rev. 2001 Oct 1;50 Suppl 1:S41-67
11576695
Eur J Med Chem. 2002 May;37(5):399-407
12008054
Lancet. 1991 Dec 14;338(8781):1488-90
1683920
Clin Pharmacol Ther. 1984 Jun;35(6):742-9
6734025
Clin Pharmacol Ther. 1996 Jul;60(1):14-24
8689807
Pharm Res. 1996 Feb;13(2):216-21
8932439
J Control Release. 2000 Mar 1;65(1-2):55-62
10699270