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Related Concept Videos

Phase II Reactions: Glucuronidation01:24

Phase II Reactions: Glucuronidation

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Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
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Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

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Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
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Bioequivalence of Drugs: Drugs with Multiple Indications01:09

Bioequivalence of Drugs: Drugs with Multiple Indications

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The concept of therapeutic equivalence (TE) in drugs with multiple indications is complex. A generic drug may be therapeutically equivalent to a brand-name product for one specific indication, but this doesn't necessarily mean it's equivalent for all other indications. Evidence of TE in one patient group and bioequivalence shown in healthy volunteers can support—but not confirm—TE for other indications. However, definitive proof requires individual clinical studies for each...
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FDA Approved Drugs: Changes to Approved Drugs01:26

FDA Approved Drugs: Changes to Approved Drugs

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Post-approval, manufacturers may modify an approved new or generic drug product. Such modifications can encompass alterations in the Active Pharmaceutical Ingredient (API), manufacturing process, formulation, batch size, manufacturing site, and container closure system (FDA Guidance for Industry, April 2004). Often, a drug product may undergo multiple changes.These modifications require careful evaluation to determine their potential impact on the drug product's identity, strength, quality,...
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Factors Influencing Drug Absorption: Drug Dissolution01:27

Factors Influencing Drug Absorption: Drug Dissolution

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The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
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Factors Affecting Protein-Drug Binding: Drug-Related Factors01:18

Factors Affecting Protein-Drug Binding: Drug-Related Factors

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Drug binding to proteins is a complex phenomenon influenced by various drug-related factors, each playing a significant role in the interaction between drugs and proteins within the body.
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...
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Related Experiment Video

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The Mesenteric Lymph Duct Cannulated Rat Model: Application to the Assessment of Intestinal Lymphatic Drug Transport
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[Drug glucuronidation and disposition in brain].

Zi-qian Zhang, Li Sheng, Yan Li

    Yao Xue Xue Bao = Acta Pharmaceutica Sinica
    |June 17, 2018
    PubMed
    Summary

    This review explores UDP-glucuronosyltransferases (UGTs) in the brain, detailing their role in drug metabolism and distribution within the central nervous system. Understanding brain UGTs is crucial for developing effective central nervous system drugs.

    Area of Science:

    • Pharmacology
    • Biochemistry
    • Neuroscience

    Background:

    • UDP-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes crucial for drug conjugation.
    • While UGTs are present in the brain, their levels are lower than in the liver.
    • Brain UGTs are inducible and inhibitable, impacting central nervous system drug distribution.

    Purpose of the Study:

    • To review the isoforms, localization, induction, inhibition, and interactions of brain UGTs.
    • To summarize the drug glucuronidation and distribution processes in the brain for selected drugs.
    • To provide insights into brain drug metabolism and distribution for CNS drug design.

    Main Methods:

    • Literature review of UDP-glucuronosyltransferases in the brain.
    • Analysis of UGTs' interaction with cytochrome P450 (CYPs) and transporters.

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  • Case summaries of drug glucuronidation and brain distribution for five drugs.

    • Main Results:

    • Brain UGTs play a significant role in the pharmacokinetics of drugs in the central nervous system.
    • UGTs, CYPs, and transporters collectively influence drug distribution across the blood-brain barrier.
    • Glucuronidation in the brain can enable or affect drug entry and action.

    Conclusions:

    • Brain UGTs are key regulators of drug metabolism and distribution in the CNS.
    • A comprehensive understanding of brain UGTs is essential for optimizing CNS drug development.
    • This review offers a valuable reference for designing future central nervous system therapeutics.