Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

Pang, K. Sandy

doi:10.1124/dmd.31.12.1507

Cited by 224 publications

(176 citation statements)

References 156 publications

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“…"правило пяти"). Повышают абсорбцию присутствие остатков азидов, аминов, салициловой кислоты [22,26].…”

Section: влияние свойств лекарстваunclassified

“…Выявлено участие в абсорбции лекарств ряда белков-транспортеров, некоторые из которых способствуют входу молекул в клетку, другие же, наоборот -выполняют "охранные" функции, не допуская в клетку инородные молекулы и осуществляя их выход через мембрану в просвет кишечника [2,26,28]. Это семейство транспортеров множественной лекарственной устойчивоcти (MDR, multidrug resistance), относящихся к классу Р-гликопротеинов (Р-gp) и АВС-белков (ATP binding cassette proteins) -MDR1 или MRP2 с массой 170 кДа.…”

Section: влияние клеточных процессов в энтероците 2221 роль белкunclassified

“…Они локализованы в плазматических мембранах многих клеток и присутствуют в основном на апикальной мембране энтероцитов, на верхушках ворсинок (рис. 3) [26]. Охарактеризован и ряд других белков-транспортеров (MRP3, PepT1, SGLT-1, NT2, GLUT1, GLUT3, GLUT5) [27].…”

Section: влияние клеточных процессов в энтероците 2221 роль белкunclassified

“…При высокой же концентрации липидов -очевидно, из-за насыщения FABР -большинство жирных кислот абсорбируется пассивно [26].…”

Section: влияние клеточных процессов в энтероците 2221 роль белкunclassified

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Bioavailability of oral drug formulations and methods for its improvement

et al. 2010

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The recent studies in nanotechnology resulted in the development of novel formulations with improved bioavailability. This is especially important for oral administered drugs as the most convenient formulations. The current review deals with the processes occurring at the gastro-intestinal (GI) tract and their influence on the drug form. The increase of bioavailability of the drug may be achieved through designing novel formulations according to the specific drug properties. They include capsules that release pharmaceutical agents at various parts of the GI tract, floating systems that prolong the presence of the drug in the GI tract, dispersed forms with surface-active soluble polymers, micelles that carry poor-soluble drugs inside their non-polar core, agents that facilitate tight junction opening, such as caprate and chitosan, and lipid-based formulations. The own data show the stimulating influence of phospholipid nanoparticles on peroral absorption of drug indomethacin in rats and on passage of transport marker and drugs through Caco-2 cell monolayer in vitro. The review summarizes current understanding of factors that influence the bioavailability of the oral drug forms, currently used models for pharmacokinetic studies, and various approaches to developing novel pharmaceutical forms that increase the bioavailability of the drugs.

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“…"правило пяти"). Повышают абсорбцию присутствие остатков азидов, аминов, салициловой кислоты [22,26].…”

Section: влияние свойств лекарстваunclassified

Section: влияние клеточных процессов в энтероците 2221 роль белкunclassified

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Bioavailability of oral drug formulations and methods for its improvement

et al. 2010

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“…The Adkison et al (2010) study was confounded because the clinical site used an enteric-coated delayed-release formulation, which allowed sulfasalazine to bypass the majority of small-intestinal BCRP (ABCG2). Mechanistically, if a delayed-release tablet is administered, then sulfasalazine will not be available until the distal small intestine (ileum)/proximal large intestine (cecum), where BCRP expression is lower on a relative expression basis (Englund et al, 2006), but more importantly, is far less concentrated per unit of surface area (Pang, 2003), such that the absorption process will be altered from that observed following administration of an immediaterelease formulation or suspension. As such, using a delayed-release formulation would also impair the ability to detect a clinical drug-drug interaction focusing on sulfasalazine BCRP-limited absorption as an endpoint.…”

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Breast Cancer Resistance Protein Substrate and Inhibition Evaluation: Why, When, and How?

et al. 2014

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We wish to thank Poirier et al. (2014) for their recently published manuscript, "The need for human breast cancer resistance protein substrate and inhibition evaluation in drug discovery and development: why, when, and how?" which attempted to contemporize many of the key concepts of breast cancer resistance protein (BCRP; ABCG2)-mediated drug disposition and drug interactions. Indeed, further contextualization of the relevance of BCRP is needed to improve the clinical translation and prediction of both perpetrator and victim drug-drug interactions related to this transporter. However, we noticed that the authors have missed some critically important concepts when referring to drugs that have complex permeability/efflux and atypical metabolism, whose disposition has been mechanistically uncovered by reverse translation (working from bedside back to the bench). These omissions resulted in the description of sulfasalazine as a poor BCRP substrate in humans, even though it is currently one of the two best available clinical BCRP probes along with rosuvastatin (Urquhart et al., 2008;Yamasaki et al., 2008;Kusuhara et al., 2012).The authors selectively used one specific clinical study as "proof" that "sulfasalazine PK was not affected in individuals with impaired BCRP function, nor when coadministered with [a BCRP inhibitor]" (Poirier et al., 2014). The study in question by Adkison et al. (2010) used oral sulfasalazine enteric-coated tablets and, in fact, surprisingly showed no significant pharmacokinetic changes with oral coadministration of the BCRP inhibitor, pantoprazole, or a significant genedose effect of the BCRP 421 C.A functional polymorphism. These results stand in stark contrast to three independent clinical studies using oral immediate-release sulfasalazine tablets and/or suspension formulation, where significant 2-to 4-fold increases in sulfasalazine exposure were observed in carriers of the BCRP 421 C.A polymorphism and during coadministration of an oral BCRP inhibitor (Urquhart et al., 2008;Yamasaki et al., 2008;Kusuhara et al., 2012), as well as three independent preclinical studies in Bcrp-knockout mice and rats (Zaher et al., 2006;Shukla et al., 2009;Zamek-Gliszczynski et al., 2012). As discussed by Adkison et al. (2010), an accidental flaw in the execution of their study demonstrated the importance of proper formulation selection (suspension or immediate release, but not extended release), rather than disproving the utility of sulfasalazine as a marker of BCRP activity in humans.Please allow us to elaborate on some subtle and important, although perhaps not apparently obvious, study caveats from the Adkison et al. (2010) study was confounded because the clinical site used an enteric-coated delayed-release formulation, which allowed sulfasalazine to bypass the majority of small-intestinal BCRP (ABCG2). Mechanistically, if a delayed-release tablet is administered, then sulfasalazine will not be available until the distal small intestine (ileum)/proximal large intestine (cecum), where BCRP expression ...

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Confectionery Products as Delivery Systems for Flavors, Health, and Oral‐Care Actives

Lakkis¹

2007

Encapsulation and Controlled Release Technologies in Food Systems

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Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

Cited by 224 publications

References 156 publications

Bioavailability of oral drug formulations and methods for its improvement

Bioavailability of oral drug formulations and methods for its improvement

Breast Cancer Resistance Protein Substrate and Inhibition Evaluation: Why, When, and How?

Confectionery Products as Delivery Systems for Flavors, Health, and Oral‐Care Actives

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