Toxicodynetics in nordiazepam and oxazepam overdoses

Sacre, Lauralicia; Ali, Salmiah Mohd; Villa, Antoine; Jouffroy, Romain; Raphalen, Jean-Herlé; Garnier, R.; Baud, Frédéric J.

doi:10.1016/j.pharma.2017.01.002

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…Oxazepam overdose is generally well-tolerated, with 44% of cases showing the absence of signs and symptoms and 41% showing drowsiness/obtundation. 1 Oxazepam level in this patient was 10 times the therapeutic trough concentration 2 and 3 times the comatose-fatal concentration. 3 The therapeutic trough concentrations are 0.1-0.4 mg/L and 2-5 mg/L for venlafaxine and pregabalin, respectively.…”

Section: Tdm Consultantmentioning

confidence: 57%

Pharmacobezoar After Venlafaxine and Oxazepam Overdose: How Pharmacokinetics Could Help?—A Grand Round

Laurent

Varvat

Goudard

et al. 2021

Therapeutic Drug Monitoring

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Section: Tdm Consultantmentioning

confidence: 57%

Pharmacobezoar After Venlafaxine and Oxazepam Overdose: How Pharmacokinetics Could Help?—A Grand Round

Laurent

Varvat

Goudard

et al. 2021

Therapeutic Drug Monitoring

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“…Many common anxiolytic medications may cause serious adverse effects such as benzodiazepine overdose . Accordingly, the administration of these medications is often based on the risk to benefit ratio, which can be narrow in certain if not many populations.…”

Section: Discussionmentioning

confidence: 99%

“…Many common anxiolytic medications may cause serious adverse effects such as benzodiazepine overdose. [16,17] Accordingly, the administration of these medications is often based on the risk to benefit ratio, which can be narrow in certain if not many populations. Co-administration of other health or dietary products that may inhibit normal CYP-mediated metabolism may increase the rate and potency of adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Effect of an anxiolytic botanical containing Souroubea sympetala and Platanus occidentalis on in-vitro diazepam human cytochrome P450-mediated metabolism

Dobson

Foster

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives A novel anxiolytic natural health product (NHP) containing Souroubea sympetala and Platanus occidentalis is available for the companion animal market and is currently being developed for clinical evaluation. Addressing the risk of potential NHP–drug interactions, this study investigated S. sympetala and P. occidentalis plant extracts, and their identified bioactive compounds, for effects on the activity of cytochrome P450 (CYP) isozymes and the metabolism of the conventional anti‐anxiety medication diazepam. Methods Souroubea sympetala and P. occidentalis extracts, a 1 : 1 blend of the two extracts, and five triterpenes were tested for inhibitory effects on human recombinant CYP3A4, CYP2D6, CYP2C9 and CYP2C19 activity using a fluorometric plate assay. Direct effects on the metabolism of diazepam were evaluated using human liver microsomes with drug and metabolite quantification by ultra‐high‐pressure liquid chromatography and mass spectroscopy. Key findings The active substances betulinic acid (BA) and ursolic acid (UA) strongly inhibited CYP3A4 activity while UA and lupeol moderately inhibited CYP2C19. All extracts exhibited strong activity against the tested isozymes at 50–100 μg/ml. BA and all plant extracts blocked the formation of major diazepam metabolites. Conclusions Betulinic acid, UA and both the extracts and blended product are expected to affect the metabolism of diazepam when given in high dose.

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“…For instance, DMdiazepam is not only a TP resulting from demethylation of diazepam but also a pharmaceutical in its own right to treat anxiety. 43 Similarly, DM-methylparaben also serves as a raw material in various industrial applications. 44 A. thaliana cells were used due to their well-defined physiological characteristics and their common use as a fast-screening tool for evaluating plant metabolism.…”

Section: Introductionmentioning

confidence: 99%

Methylation and Demethylation of Emerging Contaminants in Plants

Xiong,

Shi,

et al. 2024

Environ. Sci. Technol.

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Many contaminants of emerging concern (CECs) have reactive functional groups and may readily undergo biotransformations, such as methylation and demethylation. These transformations have been reported to occur during human metabolism and wastewater treatment, leading to the propagation of CECs. When treated wastewater and biosolids are used in agriculture, CECs and their transformation products (TPs) are introduced into soil-plant systems. However, little is known about whether transformation cycles, such as methylation and demethylation, take place in higher plants and hence affect the fate of CECs in terrestrial ecosystems. In this study, we explored the interconversion between four common CECs (acetaminophen, diazepam, methylparaben, and naproxen) and their methylated or demethylated TPs in Arabidopsis thaliana cells and whole wheat seedlings. The methylation−demethylation cycle occurred in both plant models with demethylation generally taking place at a greater degree than methylation. The transformation rate of demethylation or methylation was dependent on the bond strength of R-CH 3 , with demethylation of methylparaben or methylation of acetaminophen being more pronounced. Although not explored in this study, these interconversions may exert influences on the behavior and biological activity of CECs, particularly in terrestrial ecosystems. The study findings demonstrated the prevalence of transformation cycles between CECs and their methylated or demethylated TPs in higher plants, contributing to a more complete understanding of risks of CECs in the human-wastewater-soil-plant continuum.

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Toxicodynetics in nordiazepam and oxazepam overdoses

Cited by 10 publications

References 19 publications

Pharmacobezoar After Venlafaxine and Oxazepam Overdose: How Pharmacokinetics Could Help?—A Grand Round

Pharmacobezoar After Venlafaxine and Oxazepam Overdose: How Pharmacokinetics Could Help?—A Grand Round

Effect of an anxiolytic botanical containing Souroubea sympetala and Platanus occidentalis on in-vitro diazepam human cytochrome P450-mediated metabolism

Methylation and Demethylation of Emerging Contaminants in Plants

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