Predicting Drug Disposition via Application of BCS: Transport/Absorption/ Elimination Interplay and Development of a Biopharmaceutics Drug Disposition Classification System

Wu, Chengqing; Benet, Leslie Z.

doi:10.1007/s11095-004-9004-4

Cited by 1,230 publications

(1,012 citation statements)

References 41 publications

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“…[218][219][220] A drug product is considered rapidly dissolving when no less than 85% of the drug substance dissolves within 30 min at physiological pH. [216,217] In the modification of the BCS to the biopharmaceutics drug disposition classification system (BCDDS) proposed by Wu and Benet [221] , the definition of solubility is maintained and compounds are classified according to both their solubility and their degree of metabolism. Subsequently, Shugarts and Benet [222] have suggested that this classification may be used not only for the assessment of oral bioavailability but also for the prediction of transporter-mediated intestinal permeability.…”

Section: Estimation Of the Intracellular Drug Concentrationmentioning

confidence: 99%

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Grandvuinet

Vestergaard

Rapin³

et al. 2012

Journal of Pharmacy and Pharmacology

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Objectives This review provides an overview of intestinal human transporters for organic anions and stresses the need for standardization of the various in‐vitro methods presently employed in drug–drug interaction (DDI) investigations. Key findings Current knowledge on the intestinal expression of the apical sodium‐dependent bile acid transporter (ASBT), the breast cancer resistance protein (BCRP), the monocarboxylate transporters (MCT) 1, MCT3‐5, the multidrug resistance associated proteins (MRP) 1–6, the organic anion transporting polypetides (OATP) 2B1, 1A2, 3A1 and 4A1, and the organic solute transporter α/β (OSTα/β) has been covered along with an overview of their substrates and inhibitors. Furthermore, the many challenges in predicting clinically relevant DDIs from in‐vitro studies have been discussed with focus on intestinal transporters and the various methods for deducting in‐vitro parameters for transporters (Km/Ki/IC50, efflux ratio). The applicability of using a cut‐off value (estimated based on the intestinal drug concentration divided by the Ki or IC50) has also been considered. Summary A re‐evaluation of the current approaches for the prediction of DDIs is necessary when considering the involvement of other transporters than P‐glycoprotein. Moreover, the interplay between various processes that a drug is subject to in‐vivo such as translocation by several transporters and dissolution should be considered.

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Section: Estimation Of the Intracellular Drug Concentrationmentioning

confidence: 99%

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Grandvuinet

Vestergaard

Rapin³

et al. 2012

Journal of Pharmacy and Pharmacology

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“…In addition to filtration in the kidneys, the drug is eliminated by active tubular secretion. According to the Biopharmaceutics Drug Disposition Classification System (BDDCS) 7 , metformin, with its high solubility and poor metabolism, belongs to Class 3, suggesting that absorptive transporters are necessary for intestinal absorption to overcome its poor permeability. Furthermore, the large apparent volume of distribution of metformin indicates significant tissue uptake [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Transporters Involved in Metformin Pharmacokinetics and Treatment Response

Liang

Giacomini

2017

Journal of Pharmaceutical Sciences

128

113

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Metformin, widely used as first-line treatment for type 2 diabetes, exists primarily as a hydrophilic cation at physiological pHs. As such, membrane transporters play a substantial role in its absorption, tissues distribution, and renal elimination. Multiple organic cation transporters are determinants of the pharmacokinetics of metformin, and many of them are important in its pharmacological action, as mediators of metformin entry into target tissues. Further, a recent genomewide association study (GWAS) in a large multi-ethnic population implicated polymorphisms in SLC2A2, encoding the glucose transporter, GLUT2, as important determinants of response to metformin. Here, we describe the key transporters associated with metformin pharmacokinetics and response.

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“…Hydrochlorothiazide (HCT) (Utag, Amsterdam, Netherlands), a BCS class III drug (Wu and Benet, 2005), and celecoxib (CEL) (Sanico, Turnhout, Belgium), a BCS class II drug (Turner et al, 2012), were used as model drugs. Sorbitol (Fagron, Waregem, Belgium) was used as water-soluble plasticizer of PVOH.…”

Section: Methodsmentioning

confidence: 99%

Hot-melt extrusion of polyvinyl alcohol for oral immediate release applications

Jaeghere

Beer

Bocxlaer

et al. 2015

International Journal of Pharmaceutics

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The primary purpose of this study was to process partially hydrolyzed PVOH grades (degree of hydroxylation (DH): 33-88%) via HME and to evaluate them as carrier for oral immediate release dosage forms in order to improve the release rate of poorly water soluble drugs (i.e.HCT and CEL) via the formulation of solid dispersions. PVOH grades (DH > 70%) were able to solubilize HCT and CEL up to 15%, but required higher extrusion temperature, due to the crystalline nature of PVOH. The highest drug release rate was observed from hot-melt extruded PVOH samples with a high DH. While drug release from extrudates consisting of PVOH with a low DH was affected by ionic strength, there was no influence of pH and ionic strength on HCT release from PVOH samples with a higher DH. However, PVOH (DH > 70%) required higher extrusion temperatures, which could hamper its application for thermosensitive drugs. Therefore, the secondary purpose was to investigate the effect of sorbitol, a water-soluble plasticizer, on the thermal properties of hot-melt extruded PVOH (DH > 70%). The melting of PVOH/sorbitol mixture was required to establish molecular interactions between PVOH and sorbitol. These molecular interactions were reflected in the HME behavior: whereas an extrusion temperature of 180°C was necessary to process physical mixtures of PVOH (DH > 70%) and sorbitol, only 140°C was necessary during reextrusion (after quench cooling and cryomilling) of the PVOH/sorbitol mixture. In addition, the in vitro and in vivo dug release of plasticized PVOH was examined; whereas the CEL/PVOH/sorbitol system was able to maintain supersaturation during in vitro dissolution (0.1 N HCl) compared to Celebrex ® , the in vivo pharmacokinetic parameters (AUC 0-24h , C max and T max ) were highly comparable.

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Predicting Drug Disposition via Application of BCS: Transport/Absorption/ Elimination Interplay and Development of a Biopharmaceutics Drug Disposition Classification System

Cited by 1,230 publications

References 41 publications

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions

Transporters Involved in Metformin Pharmacokinetics and Treatment Response

Hot-melt extrusion of polyvinyl alcohol for oral immediate release applications

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