Predicting the impact of physiological and biochemical processes on oral drug bioavailability

Advanced Drug Delivery Reviews

Volumn 50, Issue SUPPL. 1, 2001, Pages

  Agoram, Balaji ^a   Woltosz, Walter S ^a   Bolger, Michael B ^a,b  

^a Simulations Plus Inc   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Carrier mediated transport and efflux; Drug absorption; In silico simulation; Saturable P450 metabolism

Indexed keywords

ABSORPTION; BIOCHEMISTRY; COMPUTER SIMULATION; DIFFERENTIAL EQUATIONS; METABOLISM; PHYSIOLOGY;

BIOAVAILABILITY;

DRUG DOSAGE;

AMPICILLIN; BETA LACTAM ANTIBIOTIC; CARRIER PROTEIN; CEFALEXIN; CIMETIDINE; CYTOCHROME P450; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; GANCICLOVIR; GLYCOPROTEIN P; LIDOCAINE; MIDAZOLAM; NALOXONE; NUCLEOSIDE ANALOG; PARACETAMOL; PEPTIDE TRANSPORTER 1; PROPRANOLOL; RANITIDINE; SAQUINAVIR; THEOPHYLLINE; UNCLASSIFIED DRUG; VALACICLOVIR; XENOBIOTIC AGENT;

COMPUTER MODEL; CONFERENCE PAPER; CONTROLLED DRUG RELEASE; DOSE TIME EFFECT RELATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG ELIMINATION; DRUG METABOLISM; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG TRANSFORMATION; DRUG TRANSPORT; FIRST PASS EFFECT; HUMAN; INFORMATION PROCESSING; INTESTINE ABSORPTION; LIVER METABOLISM; MATHEMATICAL MODEL; PREDICTION; PRIORITY JOURNAL; SIMULATION; STATISTICAL ANALYSIS;

ANIMALS; BIOLOGICAL AVAILABILITY; COMPUTER SIMULATION; HUMANS; INTESTINAL ABSORPTION; MODELS, BIOLOGICAL; PHARMACEUTICAL PREPARATIONS;

EID: 0035478779     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0169-409X(01)00179-X     Document Type: Conference Paper

References (106)

1. Molecular and physical mechanisms of first-pass extraction
2. Transport approaches to the biopharmaceutical design of oral drug delivery system: Prediction of intestinal absorption
3. Some aspects of cell permeability to weak electrolytes
4. On the mechanism of intestinal absorption of drugs
5. Theoretical model studies of drug absorption and transport in the gastrointestinal tract II
6. Theoretical model studies of drug absorption and transport in the gastrointestinal tract I
7. Theoretical model studies of drug absorption and transport in the GI tract (3)
8. Quantitative interpretation of in vivo buccal absorption of n-alkanoic acids by the physical model approach
9. Physicochemical model for dose-dependent drug absorption
10. Use of a pharmacokinetic model incorporating discontinuous gastrointestinal absorption to examine the occurrence of double peaks in oral concentration-time profiles
11. Discontinuous oral absorption pharmacokinetic model and bioavailability of 1-(2-fluoro-5-methyl-beta-l-arabinofuranosyl)uracil (L-FMAU) in rats
12. Development of predictive pharmacokinetic simulation models for drug discovery
13. Compartmental transit and dispersion model analysis of small intestinal transit flow in humans
14. A compartmental absorption and transit model for estimating oral drug absorption
15. Predicting fraction dose absorbed in humans using a macroscopic mass balance approach
16. Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: A mathematical model
17. Prediction of the plasma concentration profiles of orally administered drugs in rats on the basis of gastrointestinal transit kinetics and absorbability
18. A heterogeneous tube model of intestinal drug absorption based on probabilistic concepts
19. Heterogeneous tube model for the study of small intestinal transit flow
20. A theory of molecular absorption from the small intestine
21. Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorption-theoretical approach
22. First-pass metabolism of midazolam by the human intestine
23. Drug exsorption from blood into the gastrointestinal tract
24. The intestinal dialysis of intravenously administered phenytoin by oral activated charcoal in rats
25. Estimation of the relative contribution of the transcellular and paracellular pathway to the transport of passively absorbed drugs in the Caco-2 cell culture model
26. Membrane transport of drugs in different regions of the intestinal tract of the rat
27. Passive diffusion of weak organic electrolytes across Caco-2 cell monolayers: Uncoupling the contributions of hydrodynamic, transcellular, and paracellular barriers
28. First-pass elimination. Basic concepts and clinical consequences
29. First-pass metabolism of lidocaine in the anesthetized rabbit. Contribution of the small intestine
30. Individual variation in first-pass metabolism
31. Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data
32. Human cytochromes P-450
33. Multiple forms of human cytochrome P-450
34. Prediction of hepatic metabolic clearance based on interspecies allometric scaling techniques and in vitro-in vivo correlations
35. Interspecies scaling of interferon disposition and comparison of allometric scaling with concentration-time transformations
36. Prediction of hepatic clearance from microsomes, hepatocytes, and liver slices
37. Models of hepatic drug elimination
38. Predicting the hepatic clearance of xenobiotics in humans from in vitro data
39. The use of human hepatocytes to select compounds based on their expected hepatic extraction ratios in humans
40. Prediction of in vivo hepatic metabolic clearance of YM796 from in vitro data by use of human liver microsomes and recombinant P-450 isozymes
41. Prediction of in vivo nonlinear first-pass hepatic metabolism of YM796 from in vitro metabolic data
42. Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling
43. Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques
44. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test
45. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism
46. CYP3A gene expression in human gut epithelium
47. First-pass disposition of (-)-6-aminocarbovir in rats. I. Prodrug activation may be limited by access to enzyme
48. A new physiologically based, segregated-flow model to explain route-dependent intestinal metabolism
49. Localization, distribution, and induction of xenobiotic-metabolizing enzymes and aryl hydrocarbon hydroxylase activity within lung
50. Intestinal drug absorption and metabolism. I. Comparison of methods and models to study physiological factors of in vitro and in vivo intestinal absorption
51. The influence of diffusional barriers on presystemic gut elimination
52. Saturable small intestinal drug absorption in humans: Modeling and interpretation of cefatrizine data
53. The barrier function of CYP3A4 and P-glycoprotein in the small bowel
54. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: Implications for drug delivery and activity in cancer chemotherapy
55. Role of metabolic enzymes and efflux transporters in the absorption of drugs from the small intestine
56. Application of moment analysis to nonlinear drug disposition described by the Michaelis-Menten equation
57. Michaelis-Menten metabolite formation kinetics: Equations relating area under the curve and metabolite recovery to the administered dose
58. Theoretical Michaelis-Menten elimination model for propranolol
59. Bioavailability of sustained release propranolol formulations
60. Biology of membrane transport proteins
61. 5′-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter
62. Mapping the binding site of the small intestinal peptide carrier (PepT1) using comparative molecular field analysis
63. First-pass accumulation of salicylic acid in gut tissue after absorption in anesthetized rat
64. We may not measure the correct intestinal wall permeability coefficient of drugs: Alternative absorptive clearance concept
65. Hepatic clearance of drugs. II. Experimental evidence for acceptance of the 'well-stirred' model over the 'parallel tube' model using lidocaine in the perfused rat liver in situ preparation
66. Liver circulation and function
67. A computer simulation of the food effect: Transient changes in hepatic blood flow and Michaelis-Menten parameters as mediators of hepatic first pass metabolism and bioavailability of propranolol
68. Characterization of human small intestinal cytochromes P-450
69. Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 cells
70. Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil
71. Role of P-glycoprotein-mediated secretion in absorptive drug permeability: An approach using passive membrane permeability and affinity to P-glycoprotein
72. Pharmacokinetics of propranolol: A review
73. Dose-dependent elimination of propranolol and its major metabolites in humans
74. Propranolol: Pooled Michaelis-Menten parameters and the effect of input rate on bioavailability
75. Saturable first-pass kinetics of propranolol
76. Comparison of the pharmacokinetics of intravenous DL-propranolol in borderline and permanent hypertension
77. Plasma concentrations and bioavailability of propranolol by oral, rectal, and intravenous administration in man
78. Food effects on propranolol systemic and oral clearance: Support for a blood flow hypothesis
79. Clinical pharmacology of midazolam
80. Midazolam: The first water-soluble benzodiazepine. Pharmacology, pharmacokinetics and efficacy in insomnia and anesthesia
81. Interaction between grapefruit juice and midazolam in humans
82. Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: Effect of ketoconazole
83. Midazolam hydroxylation by human liver microsomes in vitro: Inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents
84. Midazolam alpha-hydroxylation by human liver microsomes in vitro: Inhibition by calcium channel blockers, itraconazole and ketoconazole
85. Dose dependent pharmacokinetics of midazolam
86. Clinical pharmacokinetics of digoxin 1980
87. Bioavailability of drugs: The digoxin dilemma
88. Clinical pharmacokinetics of digoxin
89. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin
90. Inhibition of the intestinal digoxin absorption and exsorption by quinidine
91. Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein
92. Clinical pharmacology of HIV protease inhibitors: Focus on saquinavir, indinavir, and ritonavir
93. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components
94. Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man
95. Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4: Potential contribution to high first-pass metabolism
96. Pharmacokinetic interactions between two human immunodeficiency virus protease inhibitors, ritonavir and saquinavir
97. Binding of the HIV protease inhibitor saquinavir to human plasma proteins
98. Immunomodulating properties of 5,20 alpha (R)-dihydroxy-6 alpha,7 alpha-epoxy-1-oxo-(5 alpha)-whitha-2,24-dienolide and solasodine
99. Pharmacokinetic comparison of pindolol with other beta-adrenoceptor-blocking agents
100. Variable first-pass elimination of propranolol following single and multiple oral doses in hypertensive patients
101. Drug-grapefruit juice interactions
102. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression
103. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine
104. Comparison of CYP2D6 content and metoprolol oxidation between microsomes isolated from human livers and small intestines
105. Modulation of P-glycoprotein expression by cytochrome P450 3A inducers in male and female rat livers