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Manthena V S Varma

Publications and source records attributed to Manthena V S Varma.

17 recordsLinked to original sources
PubMed2006

Functional role of P-glycoprotein in limiting peroral drug absorption: optimizing drug delivery.

P-glycoprotein (P-gp) associated multi-drug resistance is one of the major challenges in the chemotherapy of various cancers. On the other hand, it is now widely recognized that P-gp influences drug transport across various biological membranes. To this end, there is an increasing trend to optimize pharmacokinetics and drug delivery right from the initial stages of drug discovery by exploring all the possible mechanisms involved in 'deliverability'. Recent advances in molecular biology techniques and biochemical characterization methodologies have helped in identification of various transporters involved in absorption or secretion of drugs. P-gp, an efflux pump expressed along the gastrointestinal tract, limits the permeability of many drugs and thus affects their peroral absorption and bioavailability. A fundamental insight and thorough understanding of P-gp and its functional role in limiting drug absorption is critical to improve predictability of dynamic absorption models and aid in selection of new candidates for development, and also widen the scope of peroral delivery for 'challenging' molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies.

The present investigation attempts to increase intestinal permeability and hence absorption of biopharmaceutic classification system (BCS) Class III (cefotaxime sodium (CX)) and Class IV (cyclosporin A (CSA)) drugs by employing certain absorption enhancers. Drugs were co-perfused with sodium caprate (SC, 0.25% w/v), piperine (P, 0.004% w/v) and sodium deoxycholate (SD, 1.0% w/v) separately in rat in situ single pass intestinal perfusion model. These additives increased intestinal permeability (P(app)) and absorption rate constant (K(a)) up to two and fourfold, respectively. SC exhibited substantial absorption enhancement of both CX and CSA, while SD and P enhanced absorption of CX and CSA, respectively. Co-administration of SC significantly enhanced peroral bioavailability of CX (from 29.4 +/- 1.7 to 69.6 +/- 3.2) and CSA (from 18.4 +/- 15.6 to 49.6 +/- 25.1) in rats, while P increased bioavailability of CSA (from 18.4 +/- 15.6 to 33.1 +/- 17.7). Transmission electron microscopy of intestinal mucosa revealed that SC and SD act on lipid and protein domains of absorptive membrane. P showed no effect on intestinal P(app) and oral bioavailability of CX but has a profound effect on CSA, a known P-glycoprotein (P-gp) substrate. These results indicated that P enhances intestinal absorption of CSA by modulating P-gp mediated efflux transport. Release of lactate dehydrogenase in situ from intestinal mucosa in the presence of absorption enhancer was taken as index of its local toxicity. All the absorption enhancers showed significantly less release of LDH compared to positive control, sodium dodecyl sulfate (60% w/v). Overall, the data indicate that the features of these commonly used food ingredients or endogenous bile salts can effectively improve bioavailability of various BCS Class III and Class IV drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers.

The objective of the present investigation was to evaluate an oral 'drug delivery' approach, which involves co-administration of absorption enhancers (AEs). The representative low permeable hydrophilic (biopharmaceutic classification system (BCS) Class III) drugs used in the study comprised of cefotaxime sodium and ceftazidime pentahydrate, whereas low permeable lipophilic (BCS Class IV) drugs include cyclosporin A and lovastatin. AEs from three different chemical classes, namely, medium chain fatty acids (sodium caprylate and caprate), cyclodextrins (beta-cyclodextrin, hydroxypropyl beta-cyclodextrin) and bile salts (sodium cholate and deoxycholate) were evaluated for absorption enhancement efficacy, mechanism of action and toxicity using in vitro everted intestinal sac model. These AEs were found to enhance intestinal permeability of drugs from 2- to 27-fold. Light microscopy studies of intestinal sac incubated with AEs for 120 min revealed morphological changes in absorptive mucosa and rank order of toxicity were cyclodextrins>bile salts congruent with medium chain fatty acids. Fluorescence polarization studies indicated that brush bordered membrane vesicles labeled with lipophilic (DPH, 12AS) and hydrophilic dyes (ANS), when treated with AEs exhibited concentration and time dependent decrease in fluorescence polarization. Total protein released in presence of AEs was more than control but considerably less than EDTA (0.58% w/v), which is known to cause toxic release of proteins from cell. Overall, AEs were found to significantly enhance drug permeability by decreasing lipid membrane fluidity and/or interacting with hydrophilic domains of membrane, and has the potential to improve oral delivery.

Animals↗
PubMed2005

Relationship between lipophilicity of BCS class III and IV drugs and the functional activity of peroral absorption enhancers.

Absorption enhancers (AEs) have been shown to be specific in permeation enhancement capabilities because of which they increase absorption of some drug molecules more than others. Present study was designed to investigate the relationship between lipophilicity of drug molecules and the absorption enhancement potential of AEs. Four drug molecules of different lipophilicity were selected as model compounds, namely, cefotaxime sodium, ceftazidime pentahydrate, lovastatin and cyclosporin A. Their apparent permeability coefficients in the absence and presence of three classes of AEs (fatty acids, cyclodextrins, and bile salts) were determined using in vitro everted rat intestinal sac absorption model. Significant relationship was observed between log P of drug and absorption enhancement ratios by AEs. This relationship was found to be functionally directly or indirectly proportional depending upon nature of AE and explain the mechanism of permeation enhancement.

Animals↗
PubMed2005

pH-dependent functional activity of P-glycoprotein in limiting intestinal absorption of protic drugs 1. Simultaneous determination of quinidine and permeability markers in rat in situ perfusion samples.

A simple, specific and sensitive reversed-phase high performance liquid chromatographic (RP-HPLC) method with UV absorbance detection was developed and validated for simultaneous determination of quinidine, verapamil and passive permeability markers, in samples obtained from rat intestinal in situ single-pass perfusion studies. Chromatography was carried out on C18 column with mobile phase comprising of acetate buffer (pH 5.0) and methanol in the ratio of 40:60 (v/v) pumped at a flow rate of 0.6 ml/min and UV detection was employed at 230 and 275 nm. The average retention times for hydrochlorthiazide, frusemide, quinidine, propranolol, and verapamil were 4.9, 5.8, 6.9, 8.9 and 11.3 min, respectively. The calibration curves were linear (R(2)>0.9995) in the selected range for each analyte. The method is specific and sensitive with limit of quantification as 25 ng/ml for quinidine and verapamil. The intra- and inter-day accuracy and precision were found to be good for all the five analytes. The method was found to be reliable in permeability determination and to estimate pH-dependent P-glycoprotein (P-gp)-mediated efflux transport of quinidine. Weak bases quinidine, propranolol and verapamil showed pH-dependent permeability, where quinidine permeability increased by 3.6-fold when the luminal pH was changed from pH 4.5-7.4. Inhibition of P-gp by verapamil (200 microM) indicated that about 68% and only 35% of passive transport of quinidine was attenuated by P-gp-mediated efflux at pH 4.5 and 7.4, respectively. In conclusion, low passive transport rates of weakly basic P-gp substrates at lower pH, may lead to more accessibility of these molecules to P-gp within enterocytes thus resulting in pH-dependent functional activity of P-gp as protic drugs moves along the gastrointestinal tract.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Influence of micro-environmental pH on the gel layer behavior and release of a basic drug from various hydrophilic matrices.

The purpose of this investigation is to understand the influence of gastrointestinal (GI) pH on the gel layer formation and its dynamics for various hydrophilic/swellable matrices, in the process of developing a pH-independent controlled release system for a basic drug, oxybutynin hydrochloride (OXB). Cylindrical matrices (8-mm diameter) without and with fumaric acid, were readily prepared by direct compression. Formulations were evaluated for in vitro drug release, and gel layer dynamics was studied by viscosity measurements and texture profiling analysis. In the in vitro drug release study, OXB, which shows pH-dependent solubility, showed faster release from all the matrices in pH 1.2 medium. Release rates enhanced to a lesser extent with change of medium from pH 6.8 to pH 1.2, for HPMC polymer matrices. Anionic polymer matrices showed drastic differences in the release rates when medium was changed from pH 6.8 to pH 1.2. Addition of fumaric acid to matrices demonstrated pH-independent drug release, which was attributed to the micro-environmental pH manipulation within the hydrated gel layer. Viscosity and texture profiling studies revealed that saturation solubility of drug at swelling front play a major role in the pH-dependent drug release from HPMC matrices, while both saturation solubility and the altered gel consistency as a function of pH are involved with anionic polymer matrices. Presence of fumaric acid in HPMC matrices showed efficient retardation and pH-independent drug release. In conclusion, understanding the influence of GI physiological pH on the gel layer dynamics and manipulating the micro-environmental pH provides efficient and predictable in vivo performance from these swellable cylindrical matrices.

Drug Carriers↗
PubMed2005

Prediction of in vivo intestinal absorption enhancement on P-glycoprotein inhibition, from rat in situ permeability.

The purpose of this study is to determine the functional role of P-glycoprotein (P-gp) in intestinal absorption of drugs and to quantitatively predict the in vivo absorption enhancement on P-gp inhibition. In situ single-pass rat ileum permeability and aqueous solubility were measured for a set of 16 compounds. Permeability studies were also carried out in the presence of P-gp inhibitor to estimate the permeability enhancement on P-gp inhibition. A significant correlation was obtained between rat ileum permeability and the literature human intestinal absorption (HIA), F(a,human) (r = 0.891; p < 0.01). Compounds with permeability >0.2 x 10(-4) cm/s are completely absorbed; however, few practically insoluble compounds were overestimated with this relationship. Inhibition of P-gp increased the permeability (p < 0.05) of three moderately and three highly permeable compounds. Efflux inhibition ratio (EIR), the ratio of permeability due to P-gp-mediated efflux activity and passive permeability only, for these compounds was in the order of digoxin > paclitaxel > fexofenadine > quinidine > verapamil > cyclosporine. Integration of EIR with permeability versus F(a,human) predicted that modulation of P-gp has no significant effect on the absorption of highly permeable compounds (quinidine, verapamil, and cyclosporine A), while for moderately permeable compounds (digoxin, paclitaxel, and fexofenadine), P-gp profoundly influences the intestinal permeability. The in situ permeability in rat ileum may be used to predict the in vivo P-gp function and its quantitative contribution to intestinal drug absorption. Integration of the functional activity of P-gp with the characteristics of BCS may explain drug interactions and explore the possible pharmacokinetic advantage on P-gp inhibition.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

pH-dependent functional activity of P-glycoprotein in limiting intestinal absorption of protic drugs: kinetic analysis of quinidine efflux in situ.

The purpose of this investigation is to evaluate the quantitative contribution of pH-dependent passive permeability on the functional activity of P-glycoprotein (P-gp) in limiting intestinal absorption of weakly basic drugs, in order to include this effect in prediction models. pH-dependent octanol/buffer partition coefficient, artificial membrane permeability and in situ rat intestinal permeability of quinidine were determined in the physiological pH range of gastrointestinal tract. In situ permeability, as a function of luminal pH, was also determined in the presence of P-gp inhibitor, verapamil (500 microM). Octanol/buffer partition coefficient, transport across artificial membrane, and rat in situ permeability showed high pH-dependency. Absorption quotient (AQ), calculated from in situ permeability to express the functional activity of P-gp, declined with increase in luminal pH or increase in luminal quinidine concentration because of the increased passive permeability or saturation of P-gp. AQ was 0.57 +/- 0.02 and 0.41 +/- 0.05, while passive permeability was 0.32 +/- 0.01 x 10(-4) cm/sec and 0.43 +/- 0.02 x 10(-4) cm/sec, in jejunum and ileum, respectively, at pH 7.4. Further, apparent Michaelis-Menten constants (K(M), J(P-gp,max)) for the quinidine efflux in jejunum indicated that efflux activity was more at luminal pH 4.5 over pH 7.4. K(M) values for jejunum quinidine efflux at pH 4.5 and pH 7.4 were determined to be 77.63 +/- 10.90 and 22.86 +/- 5.22 microM, with J(P-gp,max) values of 1.47 +/- 0.08 and 0.62 +/- 0.04 nM/cm2/sec, respectively. AQ vs passive permeability showed significant relationship indicating dependency of P-gp-mediated efflux on pH-dependent passive permeability, which is dictated by ionization status for a protic or ampholytic drug. In conclusion, an orally administered drug is absorbed from various segments of intestine, which inherit difference in luminal pH, transcellular permeability and P-gp expression. In situ data suggests that pH-dependency and regional variability in passive permeability of protic substrates significantly influence their P-gp-mediated efflux and may have implications on predictions of the in vivo drug absorption.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Simultaneous determination of digoxin and permeability markers in rat in situ intestinal perfusion samples by RP-HPLC.

A simple, sensitive and specific reversed-phase high performance liquid chromatographic (RP-HPLC) assay for simultaneous determination of digoxin and permeability markers, in samples obtained from intestinal in situ single-pass perfusion studies, was developed and validated. Chromatography was carried on C-18 column with mobile phase comprising of acetate buffer (pH 3.0), acetonitrile and methanol in the ratio of 50:25:25 (v/v/v), was pumped at a flow rate of 0.5 ml/min and UV detection was employed at 220 nm. The average retention times for phenolred, propranolol, frusemide and digoxin were 9.1, 10.7, 12.9 and 15.3 min, respectively. The calibration curves were linear (R(2) > 0.998) in the range for each analyte. The method is specific and sensitive with limit of quantification of 25 ng/ml for digoxin and frusemide and 10 ng/ml for phenolred and propranolol. The method is accurate and precise with recoveries of digoxin in the range of 95.2 and 103.2% and relative standard deviation (R.S.D.) <5%. We found that this method was simple and reliable in permeability determination and to estimate the contribution of P-glycoprotein in limiting intestinal absorption.

Animals↗
PubMed2004

Rapid and selective UV spectrophotometric and RP-HPLC methods for dissolution studies of oxybutynin immediate-release and controlled-release formulations.

A new UV spectrophotometric method and a reversed-phase HPLC method were developed for quantitative evaluation of oxybutynin hydrochloride (OXB) formulations. Determination of OXB by UV spectroscopic method was based on complexation of OXB with picric acid to form picrate, which was extracted to chloroform. The picrate complex showed quantifiable absorbance at 344nm. Chromatography was carried out at 25 degrees C on a 4.6mm x 250mm 5microm cyano column that contained USP packing L10 with water:methanol:acetonitrile::48:12:40 (v/v), as mobile phase. UV detector was set at 203nm. Both methods were found to be selective, linear, accurate and precise in the specified ranges. The LOD and LOQ of HPLC method were 0.5 and 1.65microg/ml, respectively. Intra-day and inter-day variability for both methods were <2% RSD. These methods were successfully used for quantification of OXB in drug-release studies from immediate-release tablets and controlled-release (CR) formulations.

Chemistry, Pharmaceutical↗
PubMed2004

Reversed-phase liquid chromatography with ultraviolet detection for simultaneous quantitation of indinavir and propranolol from ex-vivo rat intestinal permeability studies.

A simple, rapid, sensitive and specific reversed-phase high performance liquid chromatographic (RP-HPLC) method involving ultraviolet detection (lambda = 210 nm) was developed for analysis of indinavir along with propranolol in samples obtained from ex vivo intestinal permeability studies. Chromatography was carried out on C-18 column with mobile phase comprising of phosphate buffer-acetonitrile (68:32, v/v) pumped at flow rate of 1 ml/min. The proposed method has a short run time of 12 min and involves a simple sample preparation for the purpose of reducing permeability model artifacts and to concentrate the samples. Fluorescein was used as internal standard. The proposed method has been validated with regard to specificity, detection limit, recovery, accuracy and precision. For both the drugs, method was found to be selective, linear (R(2) approximately 0.999), accurate (recovery = 100-105%) and precise (<3% R.S.D.) in the range of 2-20 microg/ml. The limit-of-detection and limit-of-quantification of the method were 40 ng/ml and 100 ng/ml for indinavir, and 30 and 80 ng/ml for propranolol, respectively. Indinavir, a widely prescribed HIV protease inhibitor, suffer from bioavailability problems where involvement of P-glycoprotein mediated drug efflux may play a significant role. The proposed method was successfully applied for intestinal permeability of indinavir to estimate the contribution of P-glycoprotein in limiting its oral bioavailability. The advantage of the developed method lies in the simultaneous determination of propranolol, a passive integrity marker, routinely employed in permeability studies and its selectivity in presence of various P-gp modulators and permeability markers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

RP-HPLC method and its validation for the determination of naloxone from a novel transdermal formulation.

The aim of the present work was to develop a simple and reliable liquid chromatographic method for the quantitative determination of naloxone (NLX) in a novel transdermal formulation. Chromatography was carried out by reversed-phase technique on a C-18 column with a mobile phase composed of methanol, acetonitrile and 50 mM phosphate buffer (pH 7) in the proportion of 40:20:40 v/v/v, at a flow rate of 1 ml/min. The UV spectrophotometric determination was performed at 220 nm. This method was found to be specific and accurate with the mean recovery of 98.72% in the range of 2-50 microg/ml, and a run time of 15 min (retention time of NLX 11.3 min). Method was applied for stability testing of novel transdermal formulation developed in our laboratory. Assay content of NLX in the formulation was determined in stability samples and compared with the control samples. Statistical analysis by Student's t-test showed no significant difference between the assay content of NLX in control and test samples at 95% confidence interval. Overall, the proposed method is highly sensitive, precise and accurate and can be used for the reliable quantitation of NLX in developed transdermal formulation with the added advantage of simple procedure.

Administration, Cutaneous↗
PubMed2004

Biopharmaceutic classification system: a scientific framework for pharmacokinetic optimization in drug research.

The tenets of biopharmaceutics, solubility and permeability, are of pivotal importance in new drug discovery and lead optimization due to the dependence of drug absorption and pharmacokinetics on these two properties. A classification system for drugs based on these two fundamental parameters, Biopharmaceutic Classification System (BCS), provides drug designer an opportunity to manipulate structure or physicochemical properties of lead candidates so as to achieve better "deliverability". Considering the facts for failure of NCEs, drug research, once concentrating on optimizing the efficacy and safety of the leads, dramatically transformed in the past two decades. With the enormous number of molecules being synthesized using combinatorial and parallel synthesis, high throughput methodologies for screening solubility and permeability has gained significant interest in pharmaceutical industry. Ultimate aim of the drug discovery scientist in pharmacokinetic optimization is to tailor the molecules so that they show the features of BCS class I without compromising on pharmacodynamics. Considerations to optimize drug delivery and pharmacokinetics right from the initial stages of drug design propelled need for "High Throughput Pharmaceutics" (HTP). In silico predictions and development of theoretical profiles for solubility and lipophilicity provides structure based biopharmaceutical optimization, while in vitro experimental models (microtitre plate assays and cell cultures) validate the predictions. Thus, biopharmaceutical characterization during drug design and early development helps in early withdrawal of molecules with insurmountable developmental problems associated with pharmacokinetic optimization.

Animals↗
PubMed2003

P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement.

Drug efflux pumps like P-glycoprotein (P-gp) and multidrug resistance (MDR) proteins were recognized to possess functional role in determining the pharmacokinetics of drugs administered by peroral as well as parenteral route. Advancements in molecular biology, to some extent, had revealed the structure, localization and functional role of P-glycoprotein and its mechanism of drug efflux. Broad substrate recognition by this protein and clinical implications of its inhibition has revolutionized cancer chemotherapy leading to design and development of novel P-glycoprotein inhibitors. In the recent times, the application of these inhibitors in improving peroral drug delivery has gained special interest. Inhibition of P-glycoprotein improves intestinal absorption and tissue distribution while reducing the substrate metabolism and its elimination. Eventually, various screening methodologies have been developed for determining the activity of P-glycoprotein, kinetics of drug transport and identification of substrates and inhibitors. In the present review, techniques used for screening P-glycoprotein inhibitors and the scope of these inhibitors in optimizing peroral drug absorption and pharmacokinetics are discussed along with a brief introduction to P-glycoprotein, its physiological function and active role in extrusion of drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Enhanced oral paclitaxel absorption with vitamin E-TPGS: effect on solubility and permeability in vitro, in situ and in vivo.

Solubility and permeability being important determinants of oral drug absorption, this study was aimed to investigate the effect of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) on the solubility and intestinal permeability of paclitaxel in vitro, in situ and in vivo, in order to estimate the absorption enhancement ability of TPGS. Aqueous solubility of paclitaxel is significantly enhanced by TPGS, where a linear increase was demonstrated above a TPGS concentration of 0.1 mg/ml. Paclitaxel demonstrated asymmetric transport across rat ileum with significantly greater (26-fold) basolateral-to-apical (B-A) permeability than that in apical-to-basolateral (A-B) direction. Presence of P-glycoprotein (P-gp) inhibitor, verapamil (200 microM), diminished asymmetric transport of paclitaxel suggesting the role of P-gp-mediated efflux. TPGS showed a concentration-dependent increase in A-B permeability and decreased B-A permeability. The maximum efflux inhibition activity was found at a minimum TPGS concentration of 0.1 mg/ml, however, further increase in TPGS concentration resulted in decreased A-B permeability with no change in B-A permeability. Thus, the maximum paclitaxel permeability attained with 0.1 mg/ml TPGS was attributed to the interplay between TPGS concentration dependent P-gp inhibition activity and miceller formation. In situ permeability studies in rats also demonstrated the role of efflux in limiting permeability of paclitaxel and inhibitory efficiency of TPGS. The plasma concentration of [14C]paclitaxel following oral administration (25 mg/kg) was significantly increased by coadministration of TPGS at a dose of 50 mg/kg in rats. Bioavailability is enhanced about 4.2- and 6.3-fold when [14C]paclitaxel was administrated with verapamil (25 mg/kg) and TPGS, respectively, as compared to [14C]paclitaxel administered alone. The effect of verapamil on oral bioavailability of [14C]paclitaxel was limited relative to the TPGS, consistent with the in vitro solubility and permeability enhancement ability of TPGS. In conclusion, the current data suggests that the coadministration of TPGS may improve the bioavailability of BCS class II-IV drugs with low solubility and/or less permeable as a result of significant P-gp-mediated efflux.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Functional role of P-glycoprotein in limiting intestinal absorption of drugs: contribution of passive permeability to P-glycoprotein mediated efflux transport.

The aim of the present study is to evaluate the quantitative contribution of passive permeability to P-glycoprotein-mediated (P-gp-mediated) efflux and the functional activity of P-gp in determining intestinal absorption of drugs, and demonstrate the relationship between efflux parameters and intestinal permeability. MDRI-MDCKII cell monolayer permeability, human intestinal absorption (HIA), and solubility data were systematically collected from the literature. Drugs were classified as a total of 63 P-gp substrates (P-gpS) and 73 nonsubstrates (NS) on the basis of efflux ratio or calcein AM inhibition and ATPase activity assays. Efflux parameters, efflux ratio (ER) and absorption quotient (AQ), were correlated to the monolayer permeability. MDRI-MDCKII cell monolayer permeability characteristics were found to be distinctly different between P-gpS and NS datasets. The ER for P-gpS was found to increase with absorptive permeability until 20 nm.s(-1), but reduced for P-gpS with high absorptive permeability. The AQ showed a linear inverse relationship with absorptive permeability. Overall, efflux parameters, ER and AQ, indicated that the transport of P-gpS with moderate passive permeability is highly attenuated by P-gp, while passive permeability overrules the P-gp-mediated efflux for high-permeability molecules. Most of the P-gpS were found towards the upper limits of molecular weight (>500) and calculated total polar surface area (>75 A(2)). This dataset indicated that unfavorable chemical features of P-gpS limit passive permeability and thus are more susceptible to P-gp-mediated efflux. In conclusion, passive permeability versus P-gp-mediated efflux determines intestinal permeability of P-gpS, where P-gp limits absorption of only moderately permeable compounds. Thus, integrating these factors with drug characteristics of the Biopharmaceutics Classification System (BCS) class better predicts the functional role of P-gp in limiting intestinal drug absorption.

ATP Binding Cassette Transporter, Subfamily B↗