Challenges in the prediction and modeling of oral absorption and bioavailability

Current Opinion in Drug Discovery and Development

Volumn 13, Issue 1, 2010, Pages 104-110

  Metcalfe, Paul D ^a   Thomas, Simon ^a  

^a CYPROTEX DISCOVERY LTD   (United Kingdom)

Author keywords

Bioavailability; Clearance; Gastrointestinal modeling; In silico modeling; In vitro in vivo correlation; Mathematical modeling; Permeability; Pharmacokinetic; Solubility

Indexed keywords

CYTOCHROME P450; GLUCURONOSYLTRANSFERASE;

ACTIVE TRANSPORT; AREA UNDER THE CURVE; COMPUTER MODEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG PENETRATION; DRUG SOLUBILITY; DRUG TRANSPORT; FIRST PASS EFFECT; HYDROGEN BOND; INTESTINE ABSORPTION; INTESTINE CELL; LIPOPHILICITY; LIVER CLEARANCE; LIVER METABOLISM; LYMPHATIC SYSTEM; MATHEMATICAL MODEL; MEMBRANE PERMEABILITY; ORAL DRUG ADMINISTRATION; PLASMA PROTEIN BINDING; PREDICTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW;

ABSORPTION; ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; HUMANS; LIVER; LYMPHATIC SYSTEM; METABOLIC CLEARANCE RATE; MODELS, BIOLOGICAL; MODELS, THEORETICAL; PREDICTIVE VALUE OF TESTS;

EID: 73849114964     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (77)

1. Amidon GL, Lennernäs H, Shah VP, Crison JR: A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res (1995) 12(3):413-420.
2. Linnankoski J, Ranta VP, Yliperttula M, Urtti A: Passive oral drug absorption can be predicted more reliably by experimental than computational models ? Fact or myth. Eur J Pharm Sci (2008) 34(2-3):129-139.
3. Yu LX, Amidon GL: A compartmental absorption and transit model for estimating oral drug absorption. Int J Pharm (1999) 186(2):119-125.
4. Thomas S, Brightman F, Gill H, Lee S, Pufong B: Simulation modelling of human intestinal absorption using Caco-2 permeability and kinetic solubility data for early drug discovery. J Pharm Sci (2008) 97(10):4557-4574.
5. Higaki K, Choe SY, Löbenberg R, Welage LS, Amidon GL: Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans. Eur J Pharm Biopharm (2008) 70(1):313-325.
6. Zhao YH, Le J, Abraham MH, Hersey A, Eddershaw PJ, Luscombe CN, Butina D, Beck G, Sherborne B, Cooper I, Platts JA: Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors. J Pharm Sci (2001) 90(6):749-784.
7. Zhao YH, Abraham MH, Hersey A, Luscombe CN: Quantitative relationship between rat intestinal absorption and Abraham descriptors. Eur J Med Chem (2003) 38(11-12): 939-947.
8. Kotecha J, Shah S, Rathod I, Subbaiah G: Prediction of oral absorption in humans by experimental immobilized artificial membrane chromatography indices and physicochemical descriptors. Int J Pharm (2008) 360(1-2):96-106.
9. Artursson P, Palm K, Luthman K: Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv Drug Deliv Rev (2001) 46(1-3):27-43. (Pubitemid 33653412)
10. Faller B: Artificial membrane assays to assess permeability. Curr Drug Metab (2008) 9(9):886-892.
11. Heikkinen AT, Mönkkönen J, Korjamo T: Kinetics of cellular retention during Caco-2 permeation experiments: Role of lysosomal sequestration and impact on permeability estimates. J Pharmacol Exp Ther (2009) 328(3):882-892.
12. Korjamo T, Heikkinen AT, Waltari P, Mönkkönen J: The asymmetry of the unstirred water layer in permeability experiments. Pharm Res (2008) 25(7):1714-1722.
13. Lakeram M, Lockley DJ, Pendlington R, Forbes B: Optimisation of the Caco-2 permeability assay using experimental design methodology. Pharm Res (2008) 25(7):1544-1551.
14. Adson A, Burton PS, Raub TJ, Barsuhn CL, Audus KL, Ho NF: Passive diffusion of weak organic electrolytes across Caco-2 cell monolayers: Uncoupling the contributions of hydrodynamic, transcellular, and paracellular barriers. J Pharm Sci (1995) 84(10):1197-1204.
15. Karlsson J, Artursson P: A new diffusion chamber system for the determination of drug permeability coefficients across the human intestinal epithelium that are independent of the unstirred water layer. Biochim Biophys Acta (1992) 1111(2):204-210.
16. Avdeef A, Bendels S, Di L, Faller B, Kansy M, Sugano K, Yamauchi Y: PAMPA -Critical factors for better predictions of absorption. J Pharm Sci (2007) 96(11):2893-2909.
17. Fossati L, Dechaume R, Hardillier E, Chevillon D, Prevost C, Bolze S, Maubon N: Use of simulated intestinal fluid for Caco-2 permeability assay of lipophilic drugs. Int J Pharm (2008) 360(1-2):148-155.
18. Badhan R, Penny J, Galetin A, Houston JB: Methodology for development of a physiological model incorporating CYP3A and P-glycoprotein for the prediction of intestinal drug absorption. J Pharm Sci (2009) 98(6):2180-2197.
19. Sugano K, Okazaki A, Sugimoto S, Tavornvipas S, Omura A, Mano T: Solubility and dissolution profile assessment in drug discovery. Drug Metab Pharmacokinet (2007) 22(4):225-254.
20. Joshi HN, Tejwani RW, Davidovich M, Sahasrabudhe VP, Jemal M, Bathala MS, Varia SA, Serajuddin AT: Bioavailability enhancement of a poorly water-soluble drug by solid dispersion in polyethylene glycol-polysorbate 80 mixture. Int J Pharm (2004) 269(1):251-258.
21. Porter CJ, Pouton CW, Cuine JF, Charman WN: Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv Drug Deliv Rev (2008) 60(6):673-691.
22. Hendriksen BA, Felix MV, Bolger MB: The composite solubility versus pH profile and its role in intestinal absorption prediction. AAPS PharmSci (2003) 5(1):E4.
23. Wei H, Löbenberg R: Biorelevant dissolution media as a predictive tool for glyburide a class II drug. Eur J Pharm Sci (2006) 29(1):45-52.
24. Sheng JJ, McNamara DP, Amidon GL: Toward an in vivo dissolution methodology: A comparison of phosphate and bicarbonate buffers. Mol Pharm (2009) 6(1):29-39.
25. Dressman JB, Reppas C: In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. Eur J Pharm Sci (2000) 11(Suppl 2):S73-S80.
26. Shono Y, Jantratid E, Janssen N, Kesisoglou F, Mao Y, Vertzoni M, Reppas C, Dressman JB: Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling. Eur J Pharm Biopharm (2009) 73(1):107-114.
27. Parrott N, Lavé T: Prediction of intestinal absorption: Comparative assessment of GASTROPLUS and IDEA. Eur J Pharm Sci (2002) 17(1-2):51-61.
28. Willmann S, Schmitt W, Keldenich J, Lippert J, Dressman JB: A physiological model for the estimation of the fraction dose absorbed in humans. J Med Chem (2004) 47(16): 4022-4031.
29. Willmann S, Schmitt W, Keldenich J, Dressman JB: A physiologic model for simulating gastrointestinal flow and drug absorption in rats. Pharm Res (2003) 20(11):1766-1771.
30. Kuentz M, Nick S, Parrott N, Röthlisberger D: A strategy for preclinical formulation development using GastroPlus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. Eur J Pharm Sci (2006) 27(1): 91-99.
31. Glaeser H, Bailey DG, Dresser GK, Gregor JC, Schwarz UI, McGrath JS, Jolicoeur E, Lee W, Leake BF, Tirona RG, Kim RB: Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharmacol Ther (2007) 81(3): 362-370.
32. Schwarz UI, Seemann D, Oertel R, Miehlke S, Kuhlisch E, Fromm MF, Kim RB, Bailey DG, Kirch W: Grapefruit juice ingestion significantly reduces talinolol bioavailability. Clin Pharmacol Ther (2005) 77(4):291-301.
33. Tam D, Tirona RG, Pang KS: Segmental intestinal transporters and metabolic enzymes on intestinal drug absorption. Drug Metab Dispos (2003) 31(4):373-383.
34. Bolger MB, Lukacova V, Woltosz WS: Simulations of the nonlinear dose dependence for substrates of influx and efflux transporters in the human intestine. AAPS J (2009) 11(2):353-363.
35. Shen DD, Kunze KL, Thummel KE: Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction. Adv Drug Deliv Rev (1997) 27(2-3):99-127.
36. Glaeser H, Drescher S, Hofmann U, Heinkele G, Somogyi AA, Eichelbaum M, Fromm MF: Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans. Clin Pharmacol Ther (2004) 76(3):230-238.
37. van Herwaarden AE, Wagenaar E, van der Kruijssen CM, van Waterschoot RA, Smit JW, Song JY, van der Valk MA, van Tellingen O, van der Hoorn JW, Rosing H, Beijnen JH et al: Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism. J Clin Invest (2007) 117(11):3583-3592.
38. von Richter O, Greiner B, Fromm MF, Fraser R, Omari T, Barclay ML, Dent J, Somogyi AA, Eichelbaum M: Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique. Clin Pharmacol Ther (2001) 70(3):217-227.
39. Higashikawa F, Murakami T, Kaneda T, Kato A, Takano M: Dose-dependent intestinal and hepatic first-pass metabolism of midazolam, a cytochrome P450 3A substrate with differently modulated enzyme activity in rats. J Pharm Pharmacol (1999) 51(1):67-72.
40. Paine MF, Shen DD, Kunze KL, Perkins JD, Marsh CL, McVicar JP, Barr DM, Gillies BS, Thummel KE: First-pass metabolism of midazolam by the human intestine. Clin Pharmacol Ther (1996) 60(1):14-24.
41. Schwarz UI, Hanso H, Oertel R, Miehlke S, Kuhlisch E, Glaeser H, Hitzl M, Dresser GK, Kim RB, Kirch W: Induction of intestinal P-glycoprotein by St John's wort reduces the oral bioavailability of talinolol. Clin Pharmacol Ther (2007) 81(5): 669-678.
42. Yang J, Jamei M, Yeo KR, Tucker GT, Rostami-Hodjegan A: Prediction of intestinal first-pass drug metabolism. Curr Drug Metab (2007) 8(7):676-684.
43. Fagerholm U: Prediction of human pharmacokinetics -Gut-wall metabolism. J Pharm Pharmacol (2007) 59(10): 1335-1343. (Pubitemid 47606447)
44. Peters SA: Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles. Clin Pharmacokinet (2008) 47(4): 245-259.
45. De Buck SS, Sinha VK, Fenu LA, Gilissen RA, Mackie CE, Nijsen MJ: The prediction of drug metabolism, tissue distribution, and bioavailability of 50 structurally diverse compounds in rat using mechanism-based absorption, distribution, and metabolism prediction tools. Drug Metab Dispos (2007) 35(4):649-659.
46. Obach RS: Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metab Dispos (1999) 27(11): 1350-1359.
47. Houston JB: Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem Pharmacol (1994) 47(9):1469-1479.
48. Lam JL, Benet LZ: Hepatic microsome studies are insufficient to characterize in vivo hepatic metabolic clearance and metabolic drug-drug interactions: Studies of digoxin metabolism in primary rat hepatocytes versus microsomes. Drug Metab Dispos (2004) 32(11):1311-1316.
49. Hallifax D, Houston JB: Methodological uncertainty in quantitative prediction of human hepatic clearance from in vitro experimental systems. Curr Drug Metab (2009) 10(3): 307-321.
50. Drochmans P, Wanson JC, Mosselmans R: Isolation and subfractionation on ficoll gradients of adult rat hepatocytes. Size, morphology, and biochemical characteristics of cell fractions. J Cell Biol (1975) 66(1):1-22.
51. Howard RB, Christensen AK, Gibbs FA, Pesch LA: The enzymatic preparation of isolated intact parenchymal cells from rat liver. J Cell Biol (1967) 35(3):675-684.
52. Wilson ZE, Rostami-Hodjegan A, Burn JL, Tooley A, Boyle J, Ellis SW, Tucker GT: Inter-individual variability in levels of human microsomal protein and hepatocellularity per gram of liver. Br J Clin Pharmacol (2003) 56(4):433-440.
53. Valentin J (Ed): Annals of the ICRP: Publication 89: Basic Anatomical and Physiological Data for Use in Radiological Protection: Reference Values. Vol 32(3-4). Elsevier Science Ltd, Oxford, UK (2002).
54. Barter ZE, Chowdry JE, Harlow JR, Snawder JE, Lipscomb JC, Rostami-Hodjegan A: Covariation of human microsomal protein per gram of liver with age: Absence of influence of operator and sample storage may justify interlaboratory data pooling. Drug Metab Dispos (2008) 36(12):2405-2409.
55. Fagerholm U: The role of permeability in drug ADME/PK, interactions and toxicity -Presentation of a permeabilitybased classification system (PCS) for prediction of ADME/PK in humans. Pharm Res (2008) 25(3):625-638.
56. Balaz S: Modeling kinetics of subcellular disposition of chemicals. Chem Rev (2009) 109(5):1793-1899.
57. Soars MG, Grime K, Sproston JL, Webborn PJ, Riley RJ: Use of hepatocytes to assess the contribution of hepatic uptake to clearance in vivo. Drug Metab Dispos (2007) 35(6):859-865.
58. Watanabe T, Maeda K, Kondo T, Nakayama H, Horita S, Kusuhara H, Sugiyama Y: Prediction of the hepatic and renal clearance of transporter substrates in rats using in vitro uptake experiments. Drug Metab Dispos (2009) 37(7):1471-1479.
59. Poirier A, Lavé T, Portmann R, Brun ME, Senner F, Kansy M, Grimm HP, Funk C: Design, data analysis, and simulation of in vitro drug transport kinetic experiments using a mechanistic in vitro model. Drug Metab Dispos (2008) 36(12):2434-2444.
60. Dimitrova MN, Matsumura H, Dimitrova A, Neitchev VZ: Interaction of albumins from different species with phospholipid liposomes. Multiple binding sites system. Int J Biol Macromol (2000) 27(3):187-194.
61. Ohtsuka I, Yokoyama S: Penetration of bovine serum albumin into dipalmitoylphosphatidylglycerol monolayers: Direct observation by atomic force microscopy. Chem Pharm Bull (2005) 53(1):42-47.
62. Tantipolphan R, Rades T, McQuillan AJ, Medlicott NJ. Adsorption of bovine serum albumin (BSA) onto lecithin studied by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Int J Pharm (2007) 337(1-2):40-47.
63. Talbert AM, Tranter GE, Holmes E, Francis PL: Determination of drug-plasma protein binding kinetics and equilibria by chromatographic profiling: Exemplification of the method using l-tryptophan and albumin. Anal Chem (2002) 74(2): 446-452.
64. Weisiger RA: Dissociation from albumin: A potentially rate-limiting step in the clearance of substances by the liver. Proc Natl Acad Sci USA (1985) 82(5):1563-1567.
65. Baker M, Parton T: Kinetic determinants of hepatic clearance: Plasma protein binding and hepatic uptake. Xenobiotica (2007) 37(10-11):1110-1134.
66. Zucker SD, Goessling W, Gollan JL: Kinetics of bilirubin transfer between serum albumin and membrane vesicles. Insight into the mechanism of organic anion delivery to the hepatocyte plasma membrane. J Biol Chem (1995) 270(3):1074-1081.
67. Zucker SD, Goessling W: Mechanism of hepatocellular uptake of albumin-bound bilirubin. Biochim Biophys Acta (2000) 1463(2):197-208.
68. Huntjens DR, Strougo A, Chain A, Metcalf A, Summerfield S, Spalding DJ, Danhof M, Della Pasqua O: Population pharmacokinetic modelling of the enterohepatic recirculation of diclofenac and rofecoxib in rats. Br J Pharmacol (2008) 153(5):1072-1084.
69. Liu X, Chism JP, LeCluyse EL, Brouwer KR, Brouwer KL: Correlation of biliary excretion in sandwich-cultured rat hepatocytes and in vivo in rats. Drug Metab Dispos (1999) 27(6):637-644. (Pubitemid 29252436)
70. Abe K, Bridges AS, Yue W, Brouwer KL: In vitro biliary clearance of angiotensin II receptor blockers and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in sandwich-cultured rat hepatocytes: Comparison with in vivo biliary clearance. J Pharmacol Exp Ther (2008) 326(3): 983-990.
71. Caliph SM, Faassen WA, Vogel GM, Porter CJ: Oral bioavailability assessment and intestinal lymphatic transport of Org 45697 and Org 46035, two highly lipophilic novel immunomodulator analogues. Curr Drug Deliv (2009) 6(4):359-366.
72. Caliph SM, Charman WN, Porter CJ: Effect of short-, medium-, and long-chain fatty acid-based vehicles on the absolute oral bioavailability and intestinal lymphatic transport of halofantrine and assessment of mass balance in lymph-cannulated and non-cannulated rats. J Pharm Sci (2000) 89(8):1073-1084.
73. Hauss DJ, Fogal SE, Ficorilli JV, Price CA, Roy T, Jayaraj AA, Keirns JJ: Lipid-based delivery systems for improving the bioavailability and lymphatic transport of a poorly water-soluble LTB4 inhibitor. J Pharm Sci (1998) 87(2):164-169.
74. Korjamo T, Kemiläinen H, Heikkinen AT, Mönkkönen J: Decrease in intracellular concentration causes the shift in Km value of efflux pump substrates. Drug Metab Dispos (2007) 35(9):1574-1579.
75. Giuliano C, Jairaj M, Zafiu CM, Laufer R: Direct determination of unbound intrinsic drug clearance in the microsomal stability assay. Drug Metab Dispos (2005) 33(9):1319-1324.
76. Peters SA, Hultin L: Early identification of drug-induced impairment of gastric emptying through physiologically based pharmacokinetic (PBPK) simulation of plasma concentration-time profiles in rat. J Pharmacokinet Pharmacodyn (2008) 35(1):1-30.
77. Poet TS, Kousba AA, Dennison SL, Timchalk C: Physiologically based pharmacokinetic/pharmacodynamic model for the organophosphorus pesticide diazinon. Neurotoxicology (2004) 25(6):1013-1030.