Predicting Human Drug Pharmacokinetics from In Vitro Permeability Using an Absorption–Disposition Model

Fliszar, Kyle A.; Hill, Brian T.; Foster, Natalie

doi:10.1002/jps.20866

Cited by 4 publications

(3 citation statements)

References 33 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One technique that might provide further insights and improved predictive performance for the in vivo situation is the recently reported utility of coupled absorption‐disposition models to anticipate the pharmacokinetics of orally administered drugs 32 , 33 . Compartments in series are used to represent stomach, intestine, and plasma spaces, and transit times are fixed to physiologically based values.…”

Section: Resultsmentioning

confidence: 99%

“…One technique that might provide further insights and improved predictive performance for the in vivo situation is the recently reported utility of coupled absorption-disposition models to anticipate the pharmacokinetics of orally administered drugs. 32,33 Compartments in series are used to represent stomach, intestine, and plasma spaces, and transit times are fixed to physiologically based values. The firstorder rate constant is calculated based on in vitro permeability, and simulated plasma concentrationtime profiles were in good agreement with pharmacokinetic profiles available in the literature for a diverse set of compounds.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Quantitative Structure‐Property Relationships Modeling to Predict In Vitro and In Vivo Binding of Drugs to the Bile Sequestrant, Colesevelam (Welchol)

Walker

Brown

Rohatagi

et al. 2009

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Quantitative structure-property relationship (QSPR) models were developed to correlate physicochemical properties of structurally unrelated drugs with extent of in vitro binding to colesevelam, and predicted values were compared with drug exposure changes in vivo following coadministration. The binding of 17 drugs to colesevelam was determined by an in vitro dissolution drug-binding assay. Data from several clinical studies in healthy volunteers to support administration of colesevelam in diabetic patients were also collected along with existing in vivo literature data and compared with in vitro results. Steric, electronic, and hydrophobic descriptors were calculated for test compounds, and univariate and partial least squares regression approaches were used to derive QSPR models to evaluate which of the molecular descriptors correlated best with in vitro binding. A quadrant analysis evaluated the correlation between predicted/actual in vitro binding results and the in vivo data. The in vitro binding assay exhibited high sensitivity, identifying those compounds with a low probability of producing relevant in vivo drug interactions. Drug lipophilicity was identified as the primary determinant of in vitro binding to colesevelam by the final univariate and partial least squares models (R(2) = 0.69 and 0.98; Q(2) = 0.48 and 0.59). The in vitro assay and in silico models represent predictive tools that may allow investigators to conduct only informative clinical drug interaction studies with colesevelam.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Quantitative Structure‐Property Relationships Modeling to Predict In Vitro and In Vivo Binding of Drugs to the Bile Sequestrant, Colesevelam (Welchol)

Walker

Brown

Rohatagi

et al. 2009

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…[9] Nevertheless, the most accurate in-vitro prediction model for incompletely absorbed drugs appears to be the 2/4/A1 cell model, which has shown its advantages in many reports, and has been proven to have a more in-vivo-like permeability than Caco-2 cells. [30][31][32][33] This model has become a favourite for western researchers in recent years; regretfully no applications have been reported for herbal medicines as yet. In addition, the everted intestinal sac is comparatively controllable and used as an intestinal in-vitro absorption model for many herbal medicines such as Coptis chinensis Franch.…”

Section: Progress Of Intestinal Absorption Of Tcmsmentioning

confidence: 99%

Intestinal absorption and bioavailability of traditional Chinese medicines: a review of recent experimental progress and implication for quality control

Liu

Lee

Sze

et al. 2013

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Objectives Experimental studies on the pharmacokinetics of traditional Chinese medicines (TCMs) have achieved great progress in recent years. This review aims to summarize the progress made on intestinal absorption and bioavailability of TCMs, and proposes the application of intestinal absorption assays as new tools for the quality and safety control of these medicines. Key findings Since only the absorbed constituents may produce possible therapeutic effect (except those that directly target the digestive tract), intestinal absorption is of utmost importance for the drug action of TCMs, which are usually taken orally. Meanwhile, complicated drug interactions may occur among the multiple ingredients in a herbal mixture. In this regard, the intestinal permeability assays not only provide useful pharmacokinetic data of TCMs, but have potential applications for quality and safety control. Moreover, knockout animals, 2/4/A1 in-vitro cell model and physiologically-based in-silico models based on the online TCM database can be quite useful for the prediction of absorption and bioavailability of TCMs. Summary A variety of in-vivo, in-vitro, in-situ and in-silico models for predicting the intestinal absorption and bioavailability can be applied to study the herbal interactions and screen appropriate biomarkers for the quality and safety control of TCMs.

show abstract

Evaluation of the Collective Impact of Passive Permeability and Active Transport on In Vivo Blood‐Brain Barrier and Gastrointestinal Drug Absorption

Volpe¹,

Shen²,

Balimane³

2014

Predictive ADMET

View full text Add to dashboard Cite

Predicting Human Drug Pharmacokinetics from In Vitro Permeability Using an Absorption–Disposition Model

Cited by 4 publications

References 33 publications

Quantitative Structure‐Property Relationships Modeling to Predict In Vitro and In Vivo Binding of Drugs to the Bile Sequestrant, Colesevelam (Welchol)

Quantitative Structure‐Property Relationships Modeling to Predict In Vitro and In Vivo Binding of Drugs to the Bile Sequestrant, Colesevelam (Welchol)

Intestinal absorption and bioavailability of traditional Chinese medicines: a review of recent experimental progress and implication for quality control

Evaluation of the Collective Impact of Passive Permeability and Active Transport on In Vivo Blood‐Brain Barrier and Gastrointestinal Drug Absorption

Contact Info

Product

Resources

About