Metabolism of diazepam in vitro

Schwartz, Morton A.; Postma, Edward

doi:10.1016/0006-2952(68)90134-2

Cited by 47 publications

(15 citation statements)

References 3 publications

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“…After recovery from acute viral hepatitis, the diazepam half-life returned almost to normal values; No statistically significant correlation was noted between the diazepam ti (a) in patients with cirrhosis or hepatitis (and drug clearance in cirrhosis) and any of the standard liver function tests. The reduced clearance of diazepam in patients with acute and chronic parenchymal liver disease suggests that this drug should be used with caution, especially on a prolonged basis, in (1)(2)(3)(4)(5). In man, the major biotransformation pathways include demethylation to Ni-desmethyldiazepam, the major metabolite detectable in the plasma, and, to a lesser extent, hydroxylation to form Ni-methyloxazepam.…”

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confidence: 99%

“…These two metabolites are hydroxylated and N-demethylated, respectively, to form oxazepam. The hydroxylated metabolites are then conjugated to their respective glucuronides, with oxazepam glucuronide as the major urinary product (1)(2)(3)(4)(5). Most studies of the plasma elimination of diazepam have been limited to data obtained after oral administration of the drug, particularly after prolonged therapy.…”

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confidence: 99%

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The Effects of Age and Liver Disease on the Disposition and Elimination of Diazepam in Adult Man

Klotz

Avant

Hoyumpa

et al. 1976

Survey of Anesthesiology

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confidence: 99%

mentioning

confidence: 99%

The Effects of Age and Liver Disease on the Disposition and Elimination of Diazepam in Adult Man

Klotz

Avant

Hoyumpa

et al. 1976

Survey of Anesthesiology

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“…16,19,20,[26][27][28][29] In contrast, it has been reported that diazepam is not metabolized in the brain. 29 If 2'-IDZ was metabolized in a manner similar to diazepam, it would be transformed to 3-hydroxylated and N-demethylated analogs in the liver (Fig. 3).…”

Section: Liver Kidney Heartmentioning

confidence: 99%

11C-labeled 2′-iododiazepam for PET studies of benzodiazepine receptors: Synthesis and comparison of biodistribution with its radioiodinated compound

et al. 1994

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For PET studies of benzodiazepine receptors, N-11C-methyl-2'-iododiazepam (2'-IDZ) was synthesized by N-methylation of its desmethyl derivative with 11C-methyl iodide, and was subsequently purified by HPLC. The labeling and purification procedures were completed within 45 min after 11C-methyl iodide trapping, and the radiochemical yield (corrected for decay) was approximately 40% based on the initial trapped radioactivity of 11C-methyl iodide. Biodistribution studies in mice demonstrated that 11C-2'-IDZ was rapidly and noticeably accumulated in the brain, and subsequently decreased with time. Accumulation was greater in the cortex than in other brain regions. When compared with 125I-2'-IDZ, the distribution was almost the same until 5 min after injection, but levels were low after 20 min. Metabolic studies indicated that the difference between these two compounds in the time course of brain radioactivity distribution may be due to N-demethylation in vivo.

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“…The metabolism of diazepam by mammalian systems involves N-demethylation to produce ND and 3-hydroxylation to produce TZ; both metabolites can then be converted to the 3-hydroxy-N-desmethyl metabolite OZ as shown in Fig. le. In addition to the above, aromatic hydroxylation at the 4' position of DZ and metabolites is common, particularly in the rat (Schwartz and Postma 1968;Rahman et al 1986;Inaba et al 1988). Standard ND, TZ and OZ metabolites were co-chromatographed with sampes from incubations with rat liver microsomes (TLC) and screening experiments (TLC and HPLC).…”

Section: Metabolism Of Probe Substratesmentioning

confidence: 99%

The screening of selected microorganisms for use as models of mammalian drug metabolism

Griffiths

Best

Jezequel

1991

Appl Microbiol Biotechnol

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Fifty fungi and two Streptomyces species were screened for their ability to metabolise the probe substrates aminopyrine, diazepam, testosterone, theophylline and warfarin. The metabolism of the 14C-labelled substrates by whole growing cells was compared with that by rat liver microsomes using TLC-autoradiography. Testosterone, warfarin and diazepam were readily metabolised by most microorganisms, and aminopyrine and theophylline were only metabolised by a few. A relationship between substrate lipophilicity and number of microorganisms able to biotransform the substrate was observed, lipophilic substrates being favoured for metabolism, analagous to mammalian cytochrome P-450. A wide variety of metabolites were produced by the screened cultures, with a significant number co-chromatographing with mammalian metabolites. Most microorganisms appeared to exhibit cytochrome P-450-type oxidative reactions such as hydroxylation and N-demethylation, similar to mammalian hepatic microsomal cytochrome P-450 systems.

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Metabolism of diazepam in vitro

Cited by 47 publications

References 3 publications

The Effects of Age and Liver Disease on the Disposition and Elimination of Diazepam in Adult Man

The Effects of Age and Liver Disease on the Disposition and Elimination of Diazepam in Adult Man

11C-labeled 2′-iododiazepam for PET studies of benzodiazepine receptors: Synthesis and comparison of biodistribution with its radioiodinated compound

The screening of selected microorganisms for use as models of mammalian drug metabolism

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