Diazepam metabolism






Understanding the Toxicology Of Diazepam

5/19/2014
03:50 | Author: Lauren Wood

Diazepam metabolism
Understanding the Toxicology Of Diazepam

The metabolism and excretion of diazepam is somewhat convoluted; the end product of diazepam metabolism (similar to the role of morphine.

Figure 3. Toxicology report showing trace levels of oxazepam, a metabolite of diazepam, which indicates semi-recent use of the latter agent.

Figure 1. Metabolic transformation pathways of diazepam into nordiazepam, temazepam, and oxazepam.

Because of its widespread use as an anxiolytic, muscle relaxant, preoperative sedative, and seizure medication, diazepam (Valium) is one of the most commonly encountered drugs on urine toxicology reports.

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Diazepam metabolism by human liver microsomes is mediated by

11/28/2014
11:40 | Author: Lauren Wood

Diazepam metabolism
Diazepam metabolism by human liver microsomes is mediated by

The primary metabolism of diazepam was studied in human liver microsomes in order to investigate the kinetics and to identify the cytochrome P450 (CYP).

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National Center for Biotechnology Information, U.S. National Library of Medicine 8600 Rockville Pike, Bethesda MD, 20894 USA.

1. The primary metabolism of diazepam was studied in human liver microsomes in order to investigate the kinetics and to identify the cytochrome P450 (CYP) isoforms responsible for the formation of the main diazepam metabolites, temazepam and N-desmethyldiazepam. 2. The formation kinetics of both metabolites were atypical and consistent with the occurrence of substrate activation. A sigmoid Vmax model equivalent to the Hill equation was used to fit the data. The degree of sigmoidicity was greater for temazepam formation than for N-desmethyldiazepam formation, so that the ratio of desmethyldiazepam:temazepam formation increased as the substrate (diazepam) concentration decreased. 3. alpha-Naphthoflavone activated both reactions but with a greater effect on temazepam formation than on N-desmethyldiazepam formation. In the presence of 25 microM alpha-naphthoflavone the kinetics for both pathways were approximated by Michaelis-Menten kinetics. 4. Studies with a series of CYP isoform selective inhibitors and with an inhibitory anti-CYP2C antibody indicated that temazepam formation was carried out mainly by CYP3A isoforms, whereas the formation of N-desmethyldiazepam was mediated by both CYP3A isoforms and S-mephenytoin hydroxylase.

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Drugs of Abuse Benzodiazepines - Mayo Medical Laboratories

11/27/2014
09:10 | Author: Lauren Wood

Diazepam metabolism
Drugs of Abuse Benzodiazepines - Mayo Medical Laboratories

Benzodiazepines are extensively metabolized, and the parent compounds are not detected in urine. Diazepam is metabolized to nordiazepam, oxazepam, and.

Chlordiazepoxide → Nordiazepam and Oxazepam.

DiazepamNordiazepam, Oxazepam, and Temazepam.

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Chapter 9 Metabolism

9/26/2014
07:40 | Author: Lauren Wood

Diazepam metabolism
Chapter 9 Metabolism

2 Both midazolam and diazepam undergo oxidation reduction or phase I reactions in the liver. 16 The fused imidazole ring of midazolam is oxidized rapidly by.

Metabolism Biotransformation of the benzodiazepines occurs in the liver. The two principal pathways involve either hepatic microsomal oxidation ( N -dealkylation or aliphatic hydroxylation) or glucuronide conjugation. 2, 15 The difference in the two pathways is significant, because oxidation is susceptible to outside influences and can be impaired by certain population characteristics (e.g., old age), disease states (e.g., hepatic cirrhosis), or the coadministration of other drugs that can impair oxidizing capacity (e.g., cimetidine).

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Benzodiazepine Pathway, Pharmacokinetics - PharmGKB

7/25/2014
05:10 | Author: Lauren Wood

Diazepam metabolism
Benzodiazepine Pathway, Pharmacokinetics - PharmGKB

For diazepam, one FDA tablet insert for diazepam indicated that there is a potentially in CYP3A4 and CYP3A5 on different BDZ metabolism have been mixed.

While the BDZs share a common template, and all bind to the GABAa receptor, they have different physiochemical properties, most notably lipid solubility, which influence their pharmacokinetics, as well as their rate of absorption and diffusion. The two principal pathways of the BDZ biotransformation involve hepatic microsomal oxidation, N -dealkylation or aliphatic hydroxylation and glucuronide conjugation [PMID: (Katzung Chapter 22). Pharmacogenomics studies of BDZs have focused on their metabolizing enzymes.

While the BDZs share a common template, they have different physiochemical properties, most notably lipid solubility, which influence their pharmacokinetics, as well as their rate of absorption and diffusion.

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