Immobilized-artificial-membrane chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability

Ong, Shaowei; Liu, Hanlan; Pidgeon, Charles

doi:10.1016/0021-9673(95)00837-3

Cited by 262 publications

(165 citation statements)

References 27 publications

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“…The most important factor for passive diffusion is the affinity between drug and membrane. The IAM chromatographic assay uses the interaction between drug and amphiphilic phospholipids covalently bound to aminopropyl silica particles (Pidgeon et al, 1995;Yang and Lundahl, 1995;Ong et al, 1996;Caldwell et al, 1998;Taillardat-Bertschinger et al, 2003), which represent the cell membrane. The membrane permeability can be predicted from the chromatographic affinity as represented by the IAM capacity factor (K IAM ).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Determination of Absorption and First-Pass Metabolism of Apicidin, a Potent Histone Deacetylase Inhibitor

et al. 2014

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Apicidin, a potential oral chemotherapeutic agent, possesses potent anti-histone-deacetylase activity. After oral administration, the total bioavailability of apicidin is known to be low (14.2%-19.3%). In the present study, we evaluated the factors contributing to the low bioavailability of apicidin by means of quantitative determination of absorption fraction and first-pass metabolism after oral administration. Apicidin was given to rats by five different routes: into the femoral vein, duodenum, superior mesenteric artery, portal vein, and carotid artery. Especially, the fraction absorbed (F X ) and the fraction that is not metabolized in the gut wall (F G ) were separated by injection of apicidin via superior mesenteric artery, which enables bypassing the permeability barrier. The F X was 45.9% 6 9.7%, the F G was 70.9% 6 8.1% and the hepatic bioavailability (F H ) was 70.6% 6 12.3%, while the pulmonary firstpass metabolism was minimal (F L = 102.8% 6 7.4%), indicating that intestinal absorption was the rate-determining step for oral absorption of apicidin. The low F X was further examined in terms of passive diffusion and transporter-mediated efflux by in vitro immobilized artificial membrane (IAM) chromatographic assay and in situ single-pass perfusion method, respectively. Although the passive diffusion potential of apicidin was high (98.01%) by the IAM assay, the in situ permeability was significantly enhanced by the presence of the P-glycoprotein (P-gp) inhibitor elacrider. These data suggest that the low bioavailability of apicidin was mainly attributed to the P-gp efflux consistent with the limited F X measured in vivo experiment.

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Section: Discussionmentioning

confidence: 99%

Quantitative Determination of Absorption and First-Pass Metabolism of Apicidin, a Potent Histone Deacetylase Inhibitor

et al. 2014

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“…Caco-2 assay has provided higher speed screening, but unfortunately the speed is still not sufficient for ultra-HTS due to its slow growth 22) and the requirement for manual assay procedures. 23) Based on the growing recognition that assays based on Caco-2 cells remain relatively low throughput methods, 4,[22][23][24][25] the parallel artificial membrane permeation assay 24) and the immobilized-artificial-membrane chromatography system 25) have also been developed to assess the affinity to the biological membrane. These systems might provide higher speed, but the data they produce are essentially similar to the partition coefficient between lipid and water.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Pharmacokinetic Properties of 222 Commercially Available Oral Drugs in Humans.

Sakaeda

Okamura

Nagata

et al. 2001

Biological & Pharmaceutical Bulletin

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This study was performed to determine the exclusion criteria that differentiate poorly absorbed drugs from good drug candidates, and to accelerate drug development by exclusion of unnecessary assessment. The molecular and pharmacokinetic properties of 222 commercially available oral drugs were tabulated and their correlations were analyzed. The exclusion criteria obtained were 1) a molecular weight of more than 500, and 2) a ClogP value of more than 5. Exceptions to molecular weight criteria were compounds with a sugar moiety, high atomic weight, and large cyclic structure. It was also suggested that being a substrate for MDR1 (P-glycoprotein) does not always result in poor bioavailability, and that drug development by chemical modification of a seed or lead compound with quantitative structure activity relationship analysis can result in lower bioavailability, higher bound fraction and lower urinary excretion, which would hamper later development processes and might result in considerable drug-drug interaction. The criteria should be adjusted according to the pharmacological profiles of the agents in question and depending on the estimated profit, but ignoring these criteria may result in a significant waste of time and money during drug development.

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“…A rapid comparison of the linear (1) and constrained (2) analogue regarding their affinity to biological membranes such as the BBB was done by IAMC that mimics membrane interactions better than partitioning in the isotropic n-octanol/water system (log P) [3,13]. The IAMC capacity factors (k' IAM ) are predictors for membrane permeability.…”

Section: Discussionmentioning

confidence: 99%

Exploratory neuropharmacological evaluation of a conformationally constrained thyrotropin-releasing hormone analogue

Teixidó¹,

Prókai-Tátrai²,

Wang³

et al. 2007

Brain Research Bulletin

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A conformationally constrained peptidomimetic derived from the endocrine and neuroactive tripeptide thyrotropin-releasing hormone (pGlu-His-Pro-NH 2 ) was synthesized by convenient solidphase organic chemistry and evaluated as a potential central nervous system agent. While this ethylene-bridged peptide analogue has been reported to lack the hormonal effect of the native peptide, we have shown in animal models that it possesses central nervous system activity characteristic of thyrotropin-releasing hormone. Compared to control, the peptidomimetic showed significant analeptic and antidepressant-like potencies. Moreover, an enhanced selectivity in antidepressant-like effect was measured when compared to that of the native peptide. Immobilized artificial membrane chromatography and in vitro metabolic stability studies also revealed that this constrained peptidomimetic has higher affinity to the blood-brain barrier than the native peptide and is metabolically stable. Consequently, this structure may be used as a template to design centrally selective and metabolically stable thyrotropin-releasing hormone analogues as potential neuropharmaceutical agents.

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Immobilized-artificial-membrane chromatography: measurements of membrane partition coefficient and predicting drug membrane permeability

Cited by 262 publications

References 27 publications

Quantitative Determination of Absorption and First-Pass Metabolism of Apicidin, a Potent Histone Deacetylase Inhibitor

Quantitative Determination of Absorption and First-Pass Metabolism of Apicidin, a Potent Histone Deacetylase Inhibitor

Molecular and Pharmacokinetic Properties of 222 Commercially Available Oral Drugs in Humans.

Exploratory neuropharmacological evaluation of a conformationally constrained thyrotropin-releasing hormone analogue

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