Pharmacologic, Pharmacokinetic, and Clinical Assessment of Illicitly Used <b>γ</b>‐Hydroxybutyrate

White, C. Michael

doi:10.1002/jcph.767

Cited by 24 publications

(45 citation statements)

References 31 publications

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“…GHB is a small uncharged molecule that easily passes the BBB penetrating cell membranes and interacting with various receptor sites (e.g. GABA-B) [110].…”

Section: Brain Tissuementioning

confidence: 99%

Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes

Busardò

Jones

2018

Clinical Toxicology

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Introduction: c-Hydroxybutyric acid is an endogenous substance, a therapeutic agent, and a recreational drug of abuse. This psychoactive substance acts as a depressant of the central nervous system and is commonly encountered in clinical and forensic practice, including impaired drivers, poisoned patients, and drug-related intoxication deaths. Objective: The aim of this review is to assist clinical and forensic practitioners with the interpretation of c-hydroxybutyric acid concentrations in blood, urine, and alternative biological specimens from living and deceased persons. Methods: The information sources used to prepare this review were PubMed, Scopus, and Web-of-Science. These databases were searched using keywords c-hydroxybutyrate (GHB), blood, urine, alternative specimens, non-conventional biological matrices, saliva, oral fluid, sweat, hair, vitreous humor (VH), brain, cerebrospinal fluid (CSF), dried blood spots (DBS), breast milk, and various combinations thereof. The resulting 4228 references were screened to exclude duplicates, which left 1980 articles for further consideration. These publications were carefully evaluated by taking into account the main aims of the review and 143 scientific papers were considered relevant. Analytical methods: The analytical methods used to determine c-hydroxybutyric acid in blood and other biological specimens make use of gas-or liquid-chromatography coupled to mass spectrometry. These hyphenated techniques are accurate, precise, and specific for their intended purposes and the lower limit of quantitation in blood and other specimens is 0.5 mg/L or less. Human pharmacokinetics: GHB is rapidly absorbed from the gut and distributes into the total body water compartment. Only a small fraction of the dose (1-2%) is excreted unchanged in the urine. The plasma elimination half-life of c-hydroxybutyric acid is short, being only about 0.5-0.9 h, which requires timely sampling of blood and other biological specimens for clinical and forensic analysis. Endogenous concentrations of GHB in blood: GHB is both an endogenous metabolite and a drug of abuse, which complicates interpretation of the laboratory results of analysis. Moreover, the concentrations of GHB in blood and other specimens tend to increase after sampling, especially in autopsy cases. This requires the use of practical "cut-off" concentrations to avoid reporting false positive results. These cutoffs are different for different biological specimen types. Concentrations of GHB in clinical and forensic practice: As a recreational drug GHB is predominantly used by young males (94%) with a mean age of 27.1 years. The mean (median) and range of concentrations in blood from apprehended drivers was 90 mg/L (82 mg/L) and 8-600 mg/L, respectively. The concentration distributions in blood taken from living and deceased persons overlapped, although the mean (median) and range of concentrations were higher in intoxication deaths; 640 mg/ L (280 mg/L) and 30-9200 mg/L, respectively. Analysis of GHB in alternative specimens: All bi...

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“…GHB is a small uncharged molecule that easily passes the BBB penetrating cell membranes and interacting with various receptor sites (e.g. GABA-B) [110].…”

Section: Brain Tissuementioning

confidence: 99%

Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes

Busardò

Jones

2018

Clinical Toxicology

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“…Despite the fact that multiple studies and discussions have been published on the cut-off level for GHB detection in biological specimens, the application of these methods to forensic cases is not simple. There are numerous factors to be considered, such as the in vivo and in vitro production of GHB in human biological specimens depending on the post-mortem interval, the time between sampling and analysis, the sample storage conditions (e.g., storage temperature, storage period, and addition of preservatives, among others), and the concomitant use of GHB with other drugs, including ethanol [ 63 , 64 ]. Although unusual, the conditions of GHBuria (γ-Hydroxybutyric aciduria) and succinic semialdehyde dehydrogenase deficiency (SSADH-D) should also be considered during diagnosis.…”

Section: Biosynthesis and Metabolism Of Ghbmentioning

confidence: 99%

Metabolic Alterations Associated with γ-Hydroxybutyric Acid and the Potential of Metabolites as Biomarkers of Its Exposure

et al. 2021

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γ-Hydroxybutyric acid (GHB) is an endogenous short chain fatty acid that acts as a neurotransmitter and neuromodulator in the mammalian brain. It has often been illegally abused or misused due to its strong anesthetic effect, particularly in drug-facilitated crimes worldwide. However, proving its ingestion is not straightforward because of the difficulty in distinguishing between endogenous and exogenous GHB, as well as its rapid metabolism. Metabolomics and metabolism studies have recently been used to identify potential biomarkers of GHB exposure. This mini-review provides an overview of GHB-associated metabolic alterations and explores the potential of metabolites for application as biomarkers of GHB exposure. For this, we discuss the biosynthesis and metabolism of GHB, analytical issues of GHB in biological samples, alterations in metabolic pathways, and changes in the levels of GHB conjugates in biological samples from animal and human studies. Metabolic alterations in organic acids, amino acids, and polyamines in urine enable discrimination between GHB-ingested animals or humans and controls. The potential of GHB conjugates has been investigated in a variety of clinical settings. Despite the recent growth in the application of metabolomics and metabolism studies associated with GHB exposure, it remains challenging to distinguish between endogenous and exogenous GHB. This review highlights the significance of further metabolomics and metabolism studies for the discovery of practical peripheral biomarkers of GHB exposure.

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“…Over the years, The Journal of Clinical Pharmacology has been a leader in publishing articles that inform clinicians about the clinical pharmacology of drugs of abuse. These articles are highly regarded and extensively downloaded 1–15 . This supplement extends that commitment to clinician education by bringing articles together in one place that address the major classes of drugs of abuse from a clinical pharmacology perspective.…”

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confidence: 99%

Drugs of Abuse: How Clinical Pharmacology Brings Clarity to the Shadows

Nafziger

White

2021

The Journal of Clinical Pharma

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Pharmacologic, Pharmacokinetic, and Clinical Assessment of Illicitly Used γ‐Hydroxybutyrate

Cited by 24 publications

References 31 publications

Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes

Interpreting γ-hydroxybutyrate concentrations for clinical and forensic purposes

Metabolic Alterations Associated with γ-Hydroxybutyric Acid and the Potential of Metabolites as Biomarkers of Its Exposure

Drugs of Abuse: How Clinical Pharmacology Brings Clarity to the Shadows

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