Property-Based Design: Optimization of Drug Absorption and Pharmacokinetics

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

1997 • 9,861 citations

A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants

1976 • 3,228 citations

Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues.

1987 • 2,788 citations

A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases

1998 • 2,483 citations

Active Transport of Sodium as the Source of Electric Current in the Short‐circuited Isolated Frog Skin.

1951 • 2,379 citations

A physiological approach to hepatic drug clearance

1975 • 1,855 citations

Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

1991 • 1,787 citations

Prediction of Physicochemical Parameters by Atomic Contributions

1999 • 1,246 citations

Physicochemical High Throughput Screening: Parallel Artificial Membrane Permeation Assay in the Description of Passive Absorption Processes

1998 • 1,205 citations

Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A.

1995 • 1,109 citations

Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms.

1998 • 1,060 citations

MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening

1999 • 895 citations

Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs.

1999 • 757 citations

Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism*

1996 • 598 citations

Property distribution of drug-related chemical databases.

2000 • 594 citations

Molecular fields in quantitative structure–permeation relationships: the VolSurf approach

2000 • 550 citations

A general pattern for substrate recognition by P‐glycoprotein

1998 • 530 citations

L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor.

1994 • 526 citations

Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists

1988 • 514 citations

Can We Learn To Distinguish between “Drug-like” and “Nondrug-like” Molecules?

1998 • 470 citations

Pharmaceutical innovation by the seven UK‐owned pharmaceutical companies (1964‐1985).

1988 • 467 citations

Estimating skin permeation. The validation of five mathematical skin permeation models

1995 • 460 citations

Correlation of Human Jejunal Permeability (in Vivo) of Drugs with Experimentally and Theoretically Derived Parameters. A Multivariate Data Analysis Approach

1998 • 436 citations

Role of P-Glycoprotein and Cytochrome P450 3A in Limiting Oral Absorption of Peptides and Peptidomimetics†

1998 • 418 citations

Predicting Blood−Brain Barrier Permeation from Three-Dimensional Molecular Structure

2000 • 418 citations

pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs.

1998 • 401 citations

Human thiopurine methyltransferase pharmacogenetics: Gene sequence polymorphisms*

1997 • 396 citations

Lipophilicity in Drug Action and Toxicology

1996 • 396 citations

A Scoring Scheme for Discriminating between Drugs and Nondrugs

1998 • 386 citations

Pharmacokinetics and pharmacodynamics of the monoamine oxidase B inhibitor mofegiline assessed during a phase I dose tolerance trial

1995 • 381 citations

Blood-Brain Barrier Permeation: Molecular Parameters Governing Passive Diffusion

1998 • 357 citations

Intestinal absorption of peptides

1975 • 353 citations

A High-Throughput Screening Method for the Determination of Aqueous Drug Solubility Using Laser Nephelometry in Microtiter Plates

2000 • 333 citations

Active secretion and enterocytic drug metabolism barriers to drug absorption

1996 • 310 citations

Selective paracellular permeability in two models of intestinal absorption: cultured monolayers of human intestinal epithelial cells and rat intestinal segments.

1993 • 306 citations

Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction

1997 • 299 citations

Designing Libraries with CNS Activity

1999 • 293 citations

A predictive algorithm for skin permeability: the effects of molecular size and hydrogen bond activity.

1995 • 287 citations

Contributions of hepatic and intestinal metabolism and P-glycoprotein to cyclosporine and tacrolimus oral drug delivery

1997 • 283 citations

First-pass metabolism of midazolam by the human intestine*

1996 • 281 citations

Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin

1996 • 280 citations

Structure–activity relationship of P-glycoprotein substrates and modifiers

2000 • 277 citations

Caco-2 monolayers in experimental and theoretical predictions of drug transport

1996 • 268 citations

Design of drugs involving the concepts and theories of drug metabolism and pharmacokinetics

1996 • 226 citations

The influence of peptide structure on transport across Caco-2 cells.

1991 • 223 citations

The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily.

1986 • 222 citations

Relevance of p‐glycoprotein for the enteral absorption of cyclosporin A: in vitro‐in vivo correlation

1996 • 221 citations

pH-Metric log P. II: Refinement of Partition Coefficients and Ionization Constants of Multiprotic Substances

1993 • 220 citations

Soft drug design: General principles and recent applications

2000 • 215 citations

Pharmacokinetic Optimization in Drug Research

2001 • 213 citations

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2000 • 210 citations

Evaluation of Dynamic Polar Molecular Surface Area as Predictor of Drug Absorption: Comparison with Other Computational and Experimental Predictors

1998 • 206 citations

Drug liposome partitioning as a tool for the prediction of human passive intestinal absorption.

1999 • 200 citations

Computation of Brain−Blood Partitioning of Organic Solutes via Free Energy Calculations

1996 • 199 citations

Comparison of intestinal permeabilities determined in multiple in vitro and in situ models: relationship to absorption in humans.

1995 • 190 citations

QSAR: Rational approaches to the design of bioactive compounds

1991 • 185 citations

A textbook of drug design and development

1991 • 184 citations

Transport of celiprolol across human intestinal epithelial (Caco‐2) cells: mediation of secretion by multiple transporters including P‐glycoprotein

1993 • 178 citations

Octanol-Water Partition: Searching for Predictive Models

1998 • 169 citations

Jejunal permeability: a comparison between the ussing chamber technique and the single-pass perfusion in humans.

1997 • 169 citations

Review of theoretical passive drug absorption models: Historical background, recent developments and limitations

1996 • 167 citations

Pharmacokinetics and metabolism in early drug discovery

1999 • 160 citations

On the Partition of Ampholytes: Application to Blood–Brain Distribution

1997 • 139 citations

The Functional Role of P-Glycoprotein in the Blood–Brain Barrier

1997 • 138 citations

Predicting human oral bioavailability of a compound: development of a novel quantitative structure-bioavailability relationship.

2000 • 136 citations

Permeability of Red Cell Membranes to Small Hydrophilic and Lipophilic Solutes

1971 • 134 citations

THE PHARMACOLOGICAL ROLE OF P-GLYCOPROTEIN IN THE INTESTINAL EPITHELIUM

1998 • 130 citations

Potential Drugs and Nondrugs: Prediction and Identification of Important Structural Features

2000 • 129 citations

Chemoinformatics – predicting the physicochemical properties of 'drug-like' molecules

2000 • 129 citations

Role of P‐glycoprotein‐mediated secretion in absorptive drug permeabiity: An approach using passive membrane permeability and affinity to P‐glycoprotein††Dedicated to Prof. B. C. Lippold on the occasion of his 60th birthday.

1999 • 129 citations

Theoretical Calculation and Prediction of Brain–Blood Partitioning of Organic Solutes Using MolSurf Parametrization and PLS Statistics

1998 • 124 citations

Potential of immobilized artificial membranes for predicting drug penetration across the blood-brain barrier.

1998 • 116 citations

Felodipine kinetics in healthy men

1985 • 114 citations

Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration- and dose-dependent absorption in vitro and in vivo.

1996 • 112 citations

Polar intermolecular interactions encoded in partition coefficients: an indirect estimation of hydrogen-bond parameters of polyfunctional solutes

1992 • 109 citations

Nifedipine: Kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration

1986 • 103 citations

Epidermal permeability–penetrant structure relationships: 4, QSAR of permeant diffusion across human stratum corneum in terms of molecular weight, H-bonding and electronic charge

2000 • 97 citations

In Vivo Pharmacokinetics of Felodipine Predicted from in Vitro Studies in Rat, Dog and Man

1986 • 95 citations

Theoretical calculation and prediction of intestinal absorption of drugs in humans using MolSurf parametrization and PLS statistics

1999 • 92 citations

Immobilized liposome chromatography of drugs for model analysis of drug-membrane interactions

1997 • 91 citations

Medicinal chemistry : principles and practice

1994 • 91 citations

Chemoinformatics — a new name for an old problem?

1999 • 88 citations

Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption.

1996 • 86 citations

Nasal delivery of peptides: an in vitro cell culture model for the investigation of transport and metabolism in human nasal epithelium

1998 • 83 citations

Structure–activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements

1999 • 77 citations

Combining in Vitro and in Vivo Pharmacokinetic Data for Prediction of Hepatic Drug Clearance in Humans by Artificial Neural Networks and Multivariate Statistical Techniques

1999 • 76 citations

Theoretical calculation and prediction of P-glycoprotein-interacting drugs using MolSurf parametrization and PLS statistics

2000 • 75 citations

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2000 • 74 citations

Use of immobilized artificial membrane chromatography for drug transport applications††Abbreviations: blood-brain barrier, BBB; bovine brain microvessel endothelial cells, BBMEC; calculated log distribution coefficient (Pallas, CompuDrug, Budapest, Hungary), ClogD; calculated log partition coefficient, ClogP; capacity factor on an IAM column, k¢IAM; capacity factor on a reversed-phase column, k¢w; log distribution coefficient, log D; immobilized artificial membrane, IAM; nonsteroidal …

1998 • 74 citations

Congeneric Behavior in Estimations of Octanol−Water Partition Coefficients by Micellar Electrokinetic Chromatography

2000 • 73 citations

Quantitative estimation of hydrogen bond contribution to permeability and absorption processes of some chemicals and drugs

1998 • 72 citations

Determination of liposome partitioning of ionizable drugs by titration

1999 • 71 citations

Lipophilicity Behavior of Model and Medicinal Compounds containing a suilfide, sulfoxide, or sulfone moiety

1997 • 70 citations

Effects of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats.

1998 • 69 citations

Interspecies scaling: A comparative study for the prediction of clearance and volume using two or more than two species

1996 • 69 citations

Benzazepinone calcium channel blockers. 2. Structure activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones

1992 • 68 citations

Combined molecular lipophilicity descriptors and their role in understanding intramolecular effects

1999 • 67 citations

Synthesis of a series of compounds related to betaxolol, a new .beta.1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases

1987 • 66 citations

Disposition and bioavailability of the β₁‐adrenoceptor antagonist talinolol in man

1995 • 62 citations

Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects.

1991 • 61 citations

Comparison of passive drug transport through Caco-2 cells and artificial membranes

1997 • 60 citations

Hydrogen Bonding Parameters for QSAR: Comparison of Indicator Variables, Hydrogen Bond Counts, Molecular Orbital and Other Parameters

1998 • 59 citations

Pharmacodynamics of variable patient compliance: implications for pharmaceutical value

1998 • 56 citations

A comparative in vitro study of percutaneous penetration of β-blockers in human skin

2000 • 55 citations

Drug Absorption II: Effect of Fasting on Intestinal Drug Absorption

1969 • 55 citations

Metabolism and structure activity data based drug design: discovery of (−) SCH 53079 an analog of the potent cholesterol absorption inhibitor (−) SCH 48461

1996 • 54 citations

Pharmacokinetics of felodipine in patients with liver disease

1989 • 53 citations

Unified Model for the Corneal Permeability of Related and Diverse Compounds with Respect to Their Physicochemical Properties

1996 • 53 citations

An Assessment of the Reaction Energetics for Cytochrome P450-Mediated Reactions

2001 • 50 citations

Absorption of angiotensin II antagonists in Ussing chambers, Caco-2, perfused jejunum loop and in vivo:

2000 • 48 citations

Comparison of levels of aldehyde oxidase with cytochrome P450 activities in human liver in vitro

1994 • 48 citations

New Targets for Antimalarial Drug Discovery

1997 • 45 citations

Spectrophotometric determination of pKa values based on a pH gradient flow-injection system

2000 • 44 citations

Renin inhibitors containing .psi.[CH2O] pseudopeptide inserts

1988 • 37 citations

Effects of structural modifications on the intestinal permeability of angiotensin II receptor antagonists and the correlation of in vitro, in situ, and in vivo absorption.

1996 • 35 citations

Improved prediction of in vivo peroral absorption from in vitro intestinal permeability using an internal standard to control for intra- and inter-rat variability.

1997 • 34 citations

Permeability of 5-fluorouracil and prodrugs in Caco-2 cell monolayers

1996 • 31 citations

Analysis of drug transport and metabolism in cell monolayer systems that have been modified by cytochrome P4503A4 cDNA-expression

2000 • 31 citations

The role of P-glycoprotein in determining the oral absorption and clearance of the NK2 antagonist, UK-224,671

2000 • 31 citations

In vitro models of the blood–brain barrier to polar permeants: Comparison of transmonolayer flux measurements and cell uptake kinetics using cultured cerebral capillary endothelial cells

1999 • 30 citations

Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers

1988 • 22 citations

Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: THE ALLOMETRIC APPROACH FOR INTERSPECIES SCALING OF PHARMACOKINETICS AND TOXICITY OF ANTI‐CANCER DRUGS

1995 • 20 citations

Insight into the lipophilicity of the aromatic N-oxide moiety.

1996 • 19 citations

Pharmacokinetic studies with atenolol in the dog

1983 • 18 citations

Untitled

2000 • 18 citations

Pharmacokinetics and metabolism of zamifenacin in mouse, rat, dog and man

1996 • 18 citations

Intrinsic and Intramolecular Lipophilicity Effects in O‐Glucuronides

1998 • 17 citations

Pharmacokinetics and metabolism of a sulphamide NK₂antagonist in rat, dog and human

2000 • 15 citations

Conformationally defined adrenergic agents. 5. Resolution, absolute configuration, and pharmacological characterization of the enantiomers of 2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline: a potent agonist at .alpha.-adrenoceptors

1987 • 15 citations

Rapid Scanning Technique for the Determination of Optimal Tandem Mass Spectrometric Conditions for Quantitative Analysis

1997 • 14 citations

In vivo non-linear intestinal permeability of celiprolol and propranolol in conscious dogs: evidence for intestinal secretion

1998 • 13 citations

The influence of lipophilicity upon the nasal absorption of a series of hexapeptides

1996 • 6 citations

Regulation of the physical and biochemical composition of blood and seminal plasma by the blood-testis barrier in Labeo ruddi and Labeo rosae (Pisces: Cyprinidae)

1992 • 5 citations

Deleted Work

1955 • 0 citations