Optimisation of oral bioavailability is a continuing challenge for the pharmaceutical and biotechnology industries. The number of potential drug candidates requiring in vivo evaluation has significantly increased with the advent of combinatorial chemistry. In addition, drug discovery programmes are increasingly forced into more lipophilic and lower solubility chemical space. To aid in the use of in vitro and in silico tools as well as reduce the number of in vivo studies required, a team-based discussion tool is proposed that provides a 'road map' to guide the selection of profiling assays that should be considered when optimising oral bioavailability. This road map divides the factors that contribute to poor oral bioavailability into two interrelated categories: absorption and metabolism. This road map provides an interface for cross discipline discussions and a systematic approach to the experimentation that drives the drug discovery process towards a common goal - acceptable oral bioavailability using minimal resources in an acceptable time frame.
Comparison of the disposition and of the metabolic pattern of Reboxetine, a new antidepressant, in the rat, dog, monkey and man
Characterization of molecular species of liver microsomal carboxylesterases of several animal species and humans
Dextromethorphan O-demethylation in liver microsomes as a prototype reaction to monitor cytochrome P-450 db1 activity
A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability
Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide after intravenous and oral administration to healthy volunteers: relationship to nonanalgesic actions
The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature
Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity
Selective paracellular permeability in two models of intestinal absorption: cultured monolayers of human intestinal epithelial cells and rat intestinal segments
Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: a mathematical model
A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma
Does fluid flow across the intestinal mucosa affect quantitative oral drug absorption? Is it time for a reevaluation?
Transport and epithelial secretion of the cardiac glycoside, digoxin, by human intestinal epithelial (Caco-2) cells
Interpatient variability in bioavailability is related to the extent of absorption: implications for bioavailability and bioequivalence studies
In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man--fact or myth
Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations
Characterization of P-glycoprotein mediated transport of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor, across MDR1-MDCK and Caco-2 cell monolayers
Synthesis of 1-substituted 3-(chloromethyl)-6-aminoindoline (6-amino-seco-CI) DNA minor groove alkylating agents and structure-activity relationships for their cytotoxicity
Design and synthesis of novel quinoxaline-2,3-dione AMPA/GlyN receptor antagonists: amino acid derivatives
Atorvastatin coadministration may increase digoxin concentrations by inhibition of intestinal P-glycoprotein-mediated secretion
Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. Part 7: structure-activity studies of bicyclic 2-pyridone-containing peptidomimetics
Capturing the crystal: prediction of enthalpy of sublimation, crystal lattice energy, and melting points of organic compounds
Design and evaluation of Lumefantrine - Oleic acid self nanoemulsifying ionic complex for enhanced dissolution
Practical anticipation of human efficacious doses and pharmacokinetics using in vitro and preclinical in vivo data
Impact of physiological, physicochemical and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oral bioavailability of rats and humans
Fabrication, modeling and characterization of multi-crosslinked methacrylate copolymeric nanoparticles for oral drug delivery
The use of ROC analysis for the qualitative prediction of human oral bioavailability from animal data
Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers
Effect of chitosan glutamate, carbomer 974P, and EDTA on the in vitro Caco-2 permeability and oral pharmacokinetic profile of acyclovir in rats
Presystemic metabolism of AZ'0908, a novel mPGES-1 inhibitor: an in vitro and in vivo cross-species comparison
Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse
Gut Wall Metabolism. Application of Pre-Clinical Models for the Prediction of Human Drug Absorption and First-Pass Elimination
Investigation of the prerequisites for the optimization of specific plasma protein binding as a strategy for the reduction of first-pass hepatic metabolism
Rat poorly predicts the combined non-absorbed and presystemically metabolized fractions in the human
Oral delivery of paclitaxel nanocrystal (PNC) with a dual Pgp-CYP3A4 inhibitor: preparation, characterization and antitumor activity
How to report and discuss ADME data in medicinal chemistry publications: in vitro data or in vivo extrapolations?
Using Physiologically Based Pharmacokinetic (PBPK) Modeling to Evaluate the Impact of Pharmaceutical Excipients on Oral Drug Absorption: Sensitivity Analyses
Projecting ADME Behavior and Drug-Drug Interactions in Early Discovery and Development: Application of the Extended Clearance Classification System
Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1 gp120
Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter (NaCT or SLC13A5)
Computational Discovery and Experimental Validation of Inhibitors of the Human Intestinal Transporter OATP2B1
Discovery of Novel Imidazo[4,5-b]pyridines as Potent and Selective Inhibitors of Phosphodiesterase 10A (PDE10A)
Discovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors
Lead identification and structure-activity relationships of heteroarylpyrazole arylsulfonamides as allosteric CC-chemokine receptor 4 (CCR4) antagonists
Recent advances in understanding prodrug transport through the SLC15 family of proton-coupled transporters.
Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis
Structural basis for prodrug recognition by the SLC15 family of proton-coupled peptide transporters.
Studying effect of glyceryl palmitostearate amount, manufacturing method and stability on polymorphic transformation and dissolution of rifaximin tablets.
Physicochemical Profiling and Comparison of Research Antiplasmodials and Advanced Stage Antimalarials with Oral Drugs.
Discovery of phosphonic diamide prodrugs and their use for the oral delivery of a series of fructose 1,6-bisphosphatase inhibitors
Rational design of a topical androgen receptor antagonist for the suppression of sebum production with properties suitable for follicular delivery
Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen receptor antagonist devoid of phototoxicity for dermatological indications
Bioinformatics in Biomedicine
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