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Related Concept Videos

Drug Concentrations: Measurements01:23

Drug Concentrations: Measurements

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Drug concentration is the quantity of a drug present in a biological sample. Measuring drug amounts in biological samples allows the clinician to understand how a drug is absorbed, distributed, metabolized, and excreted. Samples can be obtained through invasive or non-invasive methods. Invasive techniques involve surgical or parenteral interventions to gather blood, cerebrospinal fluid, or tissue biopsy. Conversely, non-invasive approaches provide samples like urine, feces, and saliva.
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Drug Distribution: Tissue Binding01:21

Drug Distribution: Tissue Binding

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Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
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Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

Physiological Pharmacokinetic Models: Assumption with Protein Binding

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Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
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Factors Affecting Drug Distribution: Tissue Permeability01:30

Factors Affecting Drug Distribution: Tissue Permeability

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The drug distribution process within the human body is a complex interplay of various physicochemical properties inherent to the drugs. These properties, including molecular size, ionization degree, partition coefficient, and stereochemical nature, significantly impact how drugs permeate biological membranes to reach their target tissues.
Small molecules with a molecular weight below 500 to 600 Daltons can easily pass through the capillary membrane, gaining access to different tissues. Larger...
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Tissue-Drug Binding: Localization of Drugs and its Significance01:24

Tissue-Drug Binding: Localization of Drugs and its Significance

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Body tissues, comprising approximately 40% of the body weight, are crucial in drug distribution and localization. These tissues can serve as drug storage sites, competing with plasma binding sites for drug molecules.
Drugs can bind to different tissue components, enhancing their distribution and localization. The factors influencing drug localization in tissues include the drug's lipophilicity, structural characteristics, tissue perfusion rate, and pH differences. These factors determine...
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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody

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Assessing the Impact of Tissue Target Concentration Data on Uncertainty in In Vivo Target Coverage Predictions.

A Tiwari1, H Luo2, X Chen3

  • 1Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Worldwide R&D, Cambridge, Massachusetts, USA. abhinav.tiwari@pfizer.com.

CPT: Pharmacometrics & Systems Pharmacology
|October 27, 2016
PubMed
Summary
This summary is machine-generated.

This study shows that measuring tissue target concentration reduces uncertainty in predicting drug coverage. More longitudinal tissue data generally decreases prediction uncertainty, improving confidence in drug discovery.

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Area of Science:

  • Pharmacology and Drug Development
  • Computational Biology
  • Biotechnology

Background:

  • Pharmacological target coverage is crucial for drug discovery and development.
  • Accurate predictions guide research from lab objectives to clinical doses.

Purpose of the Study:

  • To evaluate the impact of tissue target concentration data on confidence in site of action (SoA) coverage predictions for antibodies.
  • To identify key parameters influencing coverage prediction uncertainty.

Main Methods:

  • Utilized a site of action (SoA) model for antibodies.
  • Fitted the model with increasing amounts of synthetic tissue data.
  • Performed global sensitivity analysis to identify influential parameters.

Main Results:

  • Uncertainty in SoA coverage predictions generally decreases with more longitudinal tissue data.
  • Coverage predictions are sensitive to parameters like baseline plasma target concentration and target turnover half-life.
  • Fixing these sensitive parameters reduces uncertainty in coverage predictions.

Conclusions:

  • Measuring baseline tissue target concentration significantly reduces uncertainty in coverage predictions.
  • Identified target-related parameters that critically impact confidence in drug coverage predictions.
  • Computational analysis supports data-driven refinement of drug development strategies.