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Related Concept Videos

Drug Distribution: Tissue Binding01:21

Drug Distribution: Tissue Binding

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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Factors Affecting Drug Distribution: Organ Perfusion Rate

Drug distribution within the body is a complex process influenced by several factors, including perfusion rate, the rate at which the bloodstream transports drugs to tissue. This limitation becomes particularly significant when dealing with highly lipophilic drugs. In such cases, the rate at which the drug can move across membranes is crucial, and if the membrane is highly permeable to the drug, distribution becomes rate-limited by perfusion.
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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.
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Drug Distribution: Volume of Distribution01:25

Drug Distribution: Volume of Distribution

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.
Factors Affecting Drug Distribution: Miscellaneous Factors01:19

Factors Affecting Drug Distribution: Miscellaneous Factors

Drug distribution in the human body is a complex process influenced by various individual factors, including age, pregnancy, obesity, diet, body water composition, pH levels, and specific disease conditions.
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Drug distribution in the human body is influenced by several factors, including plasma protein concentration, body composition, blood flow, tissue-protein concentration, and tissue fluid pH. Among these, changes in plasma protein concentration and body composition due to aging significantly affect how drugs are distributed within the body. Specifically, aging is associated with a decrease in albumin levels by about 10% and an increase in α1-acid glycoprotein levels. These alterations are not...

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A High-performance Liquid Chromatography Measurement of Kynurenine and Kynurenic Acid: Relating Biochemistry to Cognition and Sleep in Rats
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Hydroxyzine distribution in postmortem cases and potential for redistribution.

Iain M McIntyre1, Phyllis Mallett, Amber Trochta

  • 1Forensic Toxicology Division, County of San Diego Medical Examiner's Office, 5570 Overland Avenue, Suite 101, San Diego, CA 92123, USA. Iain.McIntyre@sdcounty.ca.gov

Forensic Science International
|July 30, 2013
PubMed
Summary
This summary is machine-generated.

Postmortem analysis reveals that hydroxyzine concentrations in peripheral blood and liver may indicate therapeutic levels. However, hydroxyzine exhibits moderate postmortem redistribution, particularly evident in liver-to-blood ratios.

Keywords:
Central bloodHydroxyzineLiverPeripheral bloodPostmortem redistribution

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Area of Science:

  • Forensic Toxicology
  • Pharmacokinetics
  • Analytical Chemistry

Background:

  • Hydroxyzine, an antihistamine with sedative effects, is used for anxiety and emesis.
  • Understanding drug distribution in postmortem samples is crucial for accurate toxicological interpretation.

Purpose of the Study:

  • To compare postmortem hydroxyzine concentrations in peripheral blood, central blood, and liver.
  • To evaluate the potential for postmortem redistribution of hydroxyzine.

Main Methods:

  • Analysis of 10 medical examiner cases.
  • Initial screening using GC-FID, ELISA, and GC/MS.
  • Confirmation and quantification of hydroxyzine using GC-NPD.

Main Results:

  • Postmortem peripheral blood hydroxyzine concentrations ≥ 0.24 mg/L and liver concentrations ≥ 4.9 mg/kg may be therapeutic.
  • Concentration ranges: peripheral blood (0.07-3.0 mg/L), central blood (0.04-3.8 mg/L), liver (0.88-55 mg/kg).
  • Average central blood to peripheral blood ratio: 0.92. Average liver to peripheral blood ratio: 13.8.

Conclusions:

  • Hydroxyzine concentrations in peripheral blood and liver suggest potential therapeutic levels postmortem.
  • The liver-to-peripheral blood ratio indicates a moderate degree of postmortem redistribution for hydroxyzine.