γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology

Felmlee, Melanie A.; Morse, Bridget L.; Morris, Marilyn E.

doi:10.1208/s12248-020-00543-z

Cited by 40 publications

(40 citation statements)

References 129 publications

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“…5,6 Endogenous GHB is synthesized from GABA, which originates from glutamate. 7 GHB is in part degraded via the Krebs cycle through formation of succinic semialdehyde and succinic acid, and in part metabolised to GABA via GABA transaminase (Figure 1). This makes GHB both a prodrug and metabolite of GABA.…”

Section: Pharmacologymentioning

confidence: 99%

Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse

Tay¹,

WKW²,

Murnion³

2022

SAR

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Recreational gamma-hydroxybutyrate (GHB) use, although less common than other substance use, is increasingly recognised and is over-represented in emergency toxicology presentations. This narrative review summarizes GHB pharmacology, current patterns of use, potential harms and management of GHB toxicity and withdrawal. There is a complex interplay between GHB and GABA as GHB is both a prodrug and metabolite of GABA and GHB activates both GHB and GABA receptors. GHB is rapidly absorbed, with effects seen within minutes of ingestion. Metabolism is non-linear at higher doses. While GHB is listed as a controlled substance, its precursor's gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are easily available as both have industrial applications. National surveys indicate low rates of GHB use, with identification of high-risk populations in men who have sex with men and polysubstance users. GHB is one of the three drugs most commonly used in chemsex. GHB is often co-ingested with other interacting psychoactive substances. Acute toxicity is dose-dependent, and management is supportive care. Withdrawal management is generally with benzodiazepines with addition of baclofen for more severe withdrawal. Barbiturates may have a role. Titration and tapering of pharmaceutical GHB is commonly used in the Netherlands. Complicated withdrawal with delirium may require intensive care and treatment with intravenous sedation. There are high rates of relapse after withdrawal and medications for longerterm management are currently being investigated. Chronic use is associated with poorer mental, physical and sexual health, social dysfunction and poor work performance. Laboratory detection is complicated as GHB is an endogenous substance with a short halflife, and therefore not often routinely assayed in the clinical setting. Future research should focus on improving GHB detection and management of GHB withdrawal and dependence. Interventions specific for high-risk groups should be developed and assessed.

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Section: Pharmacologymentioning

confidence: 99%

Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse

Tay¹,

WKW²,

Murnion³

2022

SAR

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“…MCTs represent a major determinant in the absorption of oxybate. 24 SCFAs are transported across the gut membrane via MCTs and SMCTs. 25 The hypothesized mechanism for the food effect is that under fed conditions, dietary‐ingested SCFAs compete with oxybate for transport at MCTs and SMCTs, thereby reducing C max and AUC for both SXB and LXB.…”

Section: Discussionmentioning

confidence: 99%

“…The oxybate molecule is a butyric acid, a short‐chain fatty acid (SCFA). MCTs represent a major determinant in the absorption of oxybate 24 . SCFAs are transported across the gut membrane via MCTs and SMCTs 25 .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies

Chen

Jenkins

Zomorodi

et al. 2021

Clinical Translational Sci

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“…SCFAs in the intestinal lumen provide energy to colon cells and regulate immune response in the intestine to maintain the stability of the intestinal microecology. In addition, SCFAs can activate downstream effect molecules (e.g., MAPK, PI3K, and NLRP3) by binding to G protein-coupled receptors (e.g., GRP43, FFA2, and HCA2) on cell membranes, thus changing dendritic cells (DCs) and auxiliary T cells [64], which can also enter the cell via the transporters SLC5A8 or SLC16A1 [65,66], inhibit the activity of histone deacetylase, and increase the number of Ly6c− monocytes in the bone marrow and lungs, thereby reducing the production of neutrophils and improving allergic inflammation in the lungs. In addition to SCFAs, metabolites produced by intestinal flora, such as desaminotyrosine, indole derivatives, niacin, polyamine, urolithin A, pyruvate, and lactic acid, have anti-inflammatory and antiinfection activities.…”

Section: Gut Microbiota Metabolites and Respiratory Diseasesmentioning

confidence: 99%

Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics

Shi

et al. 2021

Canadian Journal of Infectious Diseases and Medical Microbiolog

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The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.

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γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology

Cited by 40 publications

References 129 publications

Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse

Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse

Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies

Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics

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