Prediction of drug absorption based on immobilized artificial membrane (IAM) chromatography separation and calculated molecular descriptors

Yen, Ten‐Yang; Agatonović-Kuštrin, Snežana; Evans, Allan M.; Nation, Roger L.; Ryand, J

doi:10.1016/j.jpba.2005.01.040

Cited by 44 publications

(16 citation statements)

References 42 publications

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“…Culture cell‐based models can be used not only to study drug partition into a membrane but also to elucidate the mechanisms of drug absorption and the possible binding to epithelial proteins, for example, influx and efflux transporters and enzymes 99,100. Alternatively, cell‐free in vitro methods using artificial membranes have been proposed, with reduce cost, such as the “parallel artificial membrane permeability' approach (PAMPA),96,101–112 mainly to study and predict intestinal permeability of drugs that are passively absorbed.…”

Section: Scientific Aspects Of Oral Drug Absorptionmentioning

confidence: 99%

“…In parallel, immobilized artificial membrane columns108,109 have also been used to predict membrane permeability. These artificial membranes are composed of phospholipids (e.g., phosphatidylcholine analogs or unilamellar liposomes)110 immobilized on silica surfaces and measurements of permeability are based on the different retention of drugs on the column, depending on their lipophilicity.…”

Section: Scientific Aspects Of Oral Drug Absorptionmentioning

confidence: 99%

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Antituberculosis Therapy–Induced Acute Liver Failure: Magnitude, Profile, Prognosis, and Predictors of Outcome

et al. 2010

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Antituberculosis therapy (ATT)–associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [±15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E–induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (≥10.8 mg/dL), prothrombin time (PT) prolongation (≥26 seconds), and grade III/IV encephalopathy at presentation. Conclusion: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented. Hepatology 2010

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Section: Scientific Aspects Of Oral Drug Absorptionmentioning

confidence: 99%

Section: Scientific Aspects Of Oral Drug Absorptionmentioning

confidence: 99%

Antituberculosis Therapy–Induced Acute Liver Failure: Magnitude, Profile, Prognosis, and Predictors of Outcome

et al. 2010

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“…Yen et al reported a reciprocal correlation between the negative value of the IAM retention factor (-1/k (IAM) ) and human intestinal absorption for 52 drugs (R=0.64). This correlation was further improved upon the inclusion of molecular descriptors expressing molecular size and shape, solubility and polarity (R=0.83) [55]. Kotecha et al suggested that as intestinal absorption occurs along the gastrointestinal tract and mainly in the small intestine with a pH gradient, the maximum log k w(IAM) , measured in a certain pH range (e.g.…”

Section: The Applications Of Iam Chromatography To Predict Admet Propmentioning

confidence: 99%

Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

Tsopelas

Stergiopoulos²,

Tsantili‐Kakoulidou³

2018

ADMET DMPK

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Immobilized Artificial Membrane (IAM) chromatography constitutes a valuable tool for medicinal chemists to prioritize drug candidates in early drug development. The retention on IAM stationary phases encodes lipophilicity, electrostatic and other secondary interactions contrary to traditional octanol-water partitioning. An increasing number of publications in recent years have suggested that IAM indices, including isocratic log k(IAM) or extrapolated log kw(IAM) retention factors, chromatographic hydrophobicity index CHI(IAM) or the polarity parameter Δlog kw(IAM) can successfully model the passage of xeniobiotics through biological membranes and barriers and predict pharmacokinetic properties, often in combination with additional descriptors. Examples referring to the modeling of human oral absorption, blood-brain penetration and skin partition are described. More recently, IAM chromatography has been applied to estimate toxicological endpoints in regard to drug safety, such as phospholipidosis potential, or in regard to chemical risk hazards including the bioconcentration factor and aquatic organisms’ toxicity. The promising results in both medicinal chemistry and in environmental science in combination with the speed, reproducibility and low analyte consumption suggest that a broader application of IAM chromatography in the early drug discovery process and in ecotoxicity may save time and money in initial drug candidate selection and will contribute to a reduced risk hazard of chemicals.

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“…It lacks structural similarities to cell membranes, reflecting only the hydrophobicity of a compound and is not suitable for highly polar and ionic compounds [20][21][22][23] perspectives for rapid evaluation of drug partitioning into cell membranes [24,25]. IAMs consist of phosphatidylcholine residues covalently bound to silica propylamine and consequently mimic fluid phospholipid bilayer [26][27][28][29]. This technique is an acceptable method for the prediction of membrane permeability of drugs [24,25,30] particularly for ionizable compounds due to the fact that the position of the polar compounds in biomembranes is strongly affected by electrostatic and/or hydrogen bound interaction with phospholipids [31,32].…”

Section: Introductionmentioning

confidence: 99%

A molecular chromatographic approach to analyze the cell diffusion of arginase inhibitors

Bagnost¹,

André²,

Thomassin³

et al. 2009

Journal of Chromatography B

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Prediction of drug absorption based on immobilized artificial membrane (IAM) chromatography separation and calculated molecular descriptors

Cited by 44 publications

References 42 publications

Antituberculosis Therapy–Induced Acute Liver Failure: Magnitude, Profile, Prognosis, and Predictors of Outcome

Antituberculosis Therapy–Induced Acute Liver Failure: Magnitude, Profile, Prognosis, and Predictors of Outcome

Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

A molecular chromatographic approach to analyze the cell diffusion of arginase inhibitors

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