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Related Concept Videos

Toxicokinetics: Overview01:21

Toxicokinetics: Overview

Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
Drug Toxicity: Overview01:00

Drug Toxicity: Overview

Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
Nonlinear Pharmacokinetics: Drug Elimination for IV Bolus Injection00:59

Nonlinear Pharmacokinetics: Drug Elimination for IV Bolus Injection

In pharmacokinetics, the elimination rate of a drug following a capacity-limited model is primarily controlled by two parameters: Vmax and KM. These parameters are crucial in how the drug behaves inside the body after administration.
Following the administration of a single intravenous (IV) bolus injection, we can determine the concentration of the drug in the plasma at any given time. This calculation is achieved using a specific equation that integrates the values of Vmax and KM.
We can also...
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...

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Related Experiment Video

Updated: Jun 2, 2026

Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry
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Published on: October 2, 2016

Toxicokinetics of kava.

Anthony Rowe1, Lillian Yuan Zhang, Iqbal Ramzan

  • 1Faculty of Pharmacy, University of Sydney, Bank Building (A15), Sydney, NSW 2006, Australia.

Advances in Pharmacological Sciences
|May 5, 2011
PubMed
Summary

Kava supplements, used for anxiety, can cause liver damage (hepatotoxicity) through inflammation involving liver macrophages. Individual genetic factors (pharmacogenomics) may affect the severity of this response.

Area of Science:

  • Pharmacology
  • Hepatology
  • Immunology

Background:

  • Kava (Piper methysticum) is a traditional South Pacific beverage now popular as a Western supplement for anxiety and insomnia.
  • While generally well-tolerated, kava extracts have been linked to reports of hepatotoxicity, prompting safety re-evaluations.
  • Hepatotoxicity associated with kava can manifest as acute, severe liver injury or chronic, milder forms.

Purpose of the Study:

  • To investigate the mechanisms underlying kava-induced hepatotoxicity.
  • To explore the role of inflammation and Kupffer cell activation in kava-related liver injury.
  • To consider the potential influence of pharmacogenomics on the severity of kava hepatotoxicity.

Main Methods:

  • Review of existing literature on kava consumption and adverse events.

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  • Analysis of case reports detailing kava-induced liver injury.
  • Exploration of proposed mechanisms involving kava metabolites and liver macrophages.

    • Main Results:

    • Inflammation, particularly involving liver macrophages (Kupffer cells), is implicated in both acute and chronic forms of kava hepatotoxicity.
    • Activation of Kupffer cells may occur directly or be mediated by kava metabolites.
    • Emerging evidence suggests that pharmacogenomic variations might modulate the inflammatory response and influence the clinical presentation of kava hepatotoxicity.

    Conclusions:

    • Kava-induced hepatotoxicity involves inflammatory pathways, with Kupffer cell activation playing a key role.
    • Understanding the interplay between kava metabolites, inflammation, and individual genetic makeup is crucial for assessing its liver safety.
    • Further research into pharmacogenomics may help predict and mitigate the risk of kava-related liver injury.