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Related Concept Videos

Drug Distribution: Volume of Distribution01:25

Drug Distribution: Volume of Distribution

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The volume of distribution refers to the theoretical volume necessary to contain the entire amount of an administered drug at the same concentration observed in the blood plasma. The body's intracellular fluid compartment, which makes up two-thirds of the total body water, is contrasted with the extracellular fluid compartment—comprising plasma and interstitial fluid—that accounts for one-third. The volume of distribution can vary depending on the characteristics of the drug.
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Peripheral Nervous System: Ganglia and Nerves01:24

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The Peripheral Nervous System (PNS) is a crucial component of the body's neural network, extending beyond the central nervous system (CNS) to bridge the gap between the CNS and the external environment. It encompasses nerves, ganglia, and sensory receptors.
Nerves
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Drug Distribution: Overview01:11

Drug Distribution: Overview

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Drug distribution within the body is a dynamic process involving the movement of a drug in two directions across various compartments: from the bloodstream into tissues (tissue uptake) and from tissues back into the bloodstream (tissue release or redistribution). This process is passive and primarily driven by two variables: the concentration gradient between the bloodstream and the extravascular tissues and the drug's ability to cross the cell membrane.
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Drug Distribution: Tissue Binding01:21

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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.
For...
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Factors Affecting Renal Clearance: Drug Distribution and Drug Interactions01:09

Factors Affecting Renal Clearance: Drug Distribution and Drug Interactions

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Renal clearance plays a pivotal role in drug elimination from the body and can be influenced by drug distribution and interactions. Understanding these factors is crucial in pharmacology as they impact the effectiveness and duration of drug therapy.
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Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

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Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
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The Muscle Cuff Regenerative Peripheral Nerve Interface for the Amplification of Intact Peripheral Nerve Signals
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Drug Distribution into Peripheral Nerve.

Houfu Liu1, Yan Chen2, Liang Huang2

  • 1Department of Mechanistic Safety and Disposition (H.L., X.S., T.F., S.W.), Bioanalysis, Immunogenicity and Biomarkers (L.H., X.Z., K.D.), Integrated Biological Platform Sciences (Y.C., We.Z., J.L., J.W.), Brain Delivery Technologies (Wa.Z.), Platform Technology and Science (G.C.T.), and Department of Neuroexcitation Discovery Performance Unit (G.L., W.C., T.Y., X.Y., Z.W.), GlaxoSmithKline R&D, Shanghai, People's Republic of China; and Department of Bioanalysis, Immunogenicity and Biomarkers, Platform Technology and Science, GlaxoSmithKline, Ware, United Kingdom (S.G.S.) liuhoufu79@hotmail.com.

The Journal of Pharmacology and Experimental Therapeutics
|March 8, 2018
PubMed
Summary
This summary is machine-generated.

Small molecule drugs can penetrate peripheral nerves, with brain tissue unbound fraction predicting nerve penetration. Large biologics like ProTx-II can reach the dorsal root ganglion but not the sciatic nerve or CNS.

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Area of Science:

  • Pharmacokinetics and Drug Distribution
  • Neuroscience and Drug Delivery
  • Blood-Nerve Barrier Research

Background:

  • The blood-nerve barrier (BNB) significantly impacts drug distribution into peripheral nerves, yet its influence remains poorly understood.
  • Understanding drug penetration across the BNB is crucial for developing effective treatments for peripheral neuropathies and nerve-related disorders.

Purpose of the Study:

  • To investigate the penetration of small-molecule drugs and a large peptide (ProTx-II) into peripheral nerve tissues in rats.
  • To determine the correlation between unbound drug fractions in different tissues and assess the role of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in BNB drug transport.

Main Methods:

  • Intravenous infusion of 11 small-molecule drugs and ProTx-II in rats, followed by drug concentration measurements in blood and various tissues (brain, spinal cord, sciatic nerve, DRG).
  • Equilibrium dialysis to determine unbound drug fractions in blood and tissues.
  • Assessment of P-gp/BCRP inhibition using GF120918 to evaluate their impact on imatinib distribution.

Main Results:

  • Unbound drug fraction in brain homogenate strongly correlated with that in spinal cord, sciatic nerve, and DRG, serving as a reliable surrogate.
  • Small-molecule drugs successfully penetrated the DRG and sciatic nerve.
  • P-gp and BCRP showed a limited effect on small-molecule drug distribution into peripheral nerves. ProTx-II crossed the DRG but not the sciatic nerve or CNS tissues.

Conclusions:

  • Small-molecule drugs can effectively penetrate peripheral nerve tissues, indicating the BNB is not an absolute barrier for these compounds.
  • P-gp and BCRP do not appear to be major limiting factors for small-molecule drug distribution across the BNB.
  • While large biologics like ProTx-II can access the DRG, their distribution into the sciatic nerve and CNS is restricted, highlighting size-dependent barrier penetration.