Disease relevance of Adumbran

• Benzodiazepine receptor binding in cerebrospinal fluid was significantly higher in hepatic encephalopathy patients than in controls (210 [SE 50.2] vs 40.7 [7.3] oxazepam equivalents [ng/ml]) [1].
• Unlike many other sedatives, oxazepam is eliminated normally in patients with parenchymal liver disease an therefore, on pharmacokinetic grounds, seems to be an excellent sedative for use in such persons [2].
• Normal disposition of oxazepam in acute viral hepatitis and cirrhosis [2].
• Beta-catenin mutations and protein accumulation in all hepatoblastomas examined from B6C3F1 mice treated with anthraquinone or oxazepam [3].
• Effects of renal insufficiency and age on oxazepam kinetics were assessed in 13 normal subjects (21 to 72 yr old), four patients with renal insufficiency, and eight patients on hemodialysis [4].

Psychiatry related information on Adumbran

• Oxazepam produced some rebound insomnia, consisting of about an hour's reduction of polysomnographically defined sleep, but without gross mood disturbance or the patients' awareness of sleep loss [5].
• Fifty-nine elderly residents of long-term care facilities who had DSM-III diagnoses of dementia were studied in an 8-week randomized, double-blind comparison trial of haloperidol, oxazepam, and diphenhydramine to test the efficacy of these agents in the treatment of clinically significant behavioral disturbances in patients with dementia [6].
• Clonidine and oxazepam did not significantly decrease withdrawal symptoms, nor was either drug self-administered significantly more than placebo [7].
• Interacting effects of oxazepam in late pregnancy and fostering procedure on mouse maternal behavior [8].
• A double-blind comparison of lorazepam and oxazepam in psychomotor retardation and mutism [9].

High impact information on Adumbran

• Long v short half-life benzodiazepines in the elderly. Kinetics and clinical effects of diazepam and oxazepam [10].
• The purpose of this study was to compare the effects of LO and oxazepam (OX), benzodiazepines with comparable pharmacokinetics, on psychomotor retardation and mutism associated with psychiatric disorder [9].
• The increases in glucuronidation were at the expense of other pathways of metabolism, and there were no significant changes in the metabolic clearance rates of acetaminophen and oxazepam [11].
• Self-administration of clonidine, oxazepam, and hydromorphone by patients undergoing methadone detoxification [7].
• Cabbage and brussels sprouts induced a 17% decrease in mean plasma AUC and a 19% increase in mean metabolic clearance rate for oxazepam, but there was no change in mean plasma t1/2 for this drug, nor was there a change in ratio in plasma of oxazepam glucuronide to oxazepam [12].

Chemical compound and disease context of Adumbran

• In addition, the apparent volume of distribution of oxazepam, its plasma binding, blood/plasma ratio, and the rate of urinary excretion of oxazepam, predominantly as the glucuronide, were comparable (p greater than 0.05) in the two groups of patients with liver disease and their respective controls [2].
• Chlordiazepoxide and oxazepam disposition in cirrhosis [13].
• When diazepam was given for sedative purpose in neonates and infants, the in-vivo urinary excretion of desmethyl diazepam, temazepam and oxazepam was extremely low in 1-2 day newborns (less than 5 nmol metabolites excreted in 24 h per kg body weight) and developed in the first week after birth [14].
• The rate of glucuronidation of paracetamol and oxazepam is increased in hyperthyroidism [15].
• The results are also compatible with an analysis of epidemiological data showing that diazepam abuse uniformly exceeds oxazepam abuse on seven epidemiological measures of drug abuse [16].

Biological context of Adumbran

• Oxazepam esters. 1. Correlation between hydrolysis rates and brain appearance of oxazepam [17].
• These results, together with those from the National Toxicology Program study showing no evidence of cytotoxicity or genotoxicity by oxazepam, suggest that oxazepam preferentially promotes cells that have activating lesions other than ras [18].
• Bioequivalence studies in the elderly: a pilot study of two oxazepam dosage forms [19].
• The effects of 10 and 30 mg oxazepam were assessed at pretest and 2.5 hours after drug administration on: (a) saccadic eye movements as proxy for the sedative effect, (b) acoustic startle response (ASR) as proxy for the anxiolytic effects, (c) memory, (d) reaction time tasks, and (e) subjective measurements [20].
• These gene expression changes were confirmed for the livers from the oxazepam-treated mice in the present study, but were not good early markers for all the carcinogens in this study [21].

Anatomical context of Adumbran

• 9. A survey of the in vitro formation of oxazepam glucuronides by microsomes from 37 human livers also showed that 10% of the livers displayed an abnormally high apparent Michaelis constant (Km) for the formation of the (S) glucuronide, but not of the (R) glucuronide [22].
• Due to the absence of any navigational impairment, data suggest that prenatal exposure to oxazepam exerts long-term influence on adult learning capacities primarily through interaction with brain systems located outside the hippocampus [23].
• The effects of sodium fluoride (NaF) and cobalt chloride (CoCl2) on the enantioselective hydrolysis of racemic oxazepam 3-acetate (rac-OXA) by microsomal and cytosolic esterases in rat intestinal mucosa were studied [24].
• Outbred CD-1 mouse fetuses were administered either oxazepam (OX, 15 mg/kg) or vehicle twice a day on embryonic days 12-16 and fostered at birth to untreated dams [25].
• Inhibition of morphine glucuronidation by oxazepam in human fetal liver microsomes [26].

Associations of Adumbran with other chemical compounds

• Lorazepam and oxazepam kinetics in women on low-dose oral contraceptives [27].
• These considerations together with that of the short half-life of oxazepam (median, 6.1 hr) suggest that oxazepam may be the drug of choice if benzodiazepine therapy is used for patients taking disulfiram [28].
• Potential interferences with the internal standard (N-desmethyldoxepin) and nortryptaline were oxazepam and N-desmethyldiazepam, respectively, as shown by mass spectrometry [29].
• Previously we demonstrated that the mouse liver tumor response to the non-genotoxic carcinogens oxazepam and Wyeth-14,643 involved more differences than similarities in changes in early gene expression [21].
• Phenobarbital and oxazepam elevated both thresholds, but the effect on TGS was more pronounced [30].

Gene context of Adumbran

• At 100 micromol/l D-aspartate oxazepam stimulated EAAT1-mediated uptake up to 150% in a dose dependent manner, whereas the inhibition by low concentrations of diazepam was attenuated [31].
• Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9 [32].
• Diazepam (100 microM, 2.9 mg/100 ml), added to a 100-ml CYP3A4 bioreactor, was converted to temazepam (1.1 mg), N-demethyldiazepam (0.35 mg), and oxazepam (0.15 mg) [33].
• Low frequency of H-ras mutations in hepatocellular adenomas and carcinomas and in hepatoblastomas from B6C3F1 mice exposed to oxazepam in the diet [18].
• UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver [34].

Analytical, diagnostic and therapeutic context of Adumbran

• The inpatient program combined comprehensive psychiatric and medical evaluation, detoxification with oxazepam, and the initiation of rehabilitation treatment [35].
• The outpatients were evaluated medically and psychiatrically and then were prescribed decreasing doses of oxazepam on the basis of daily clinic visits [35].
• Nine subjects were tested before, 1, 3, 7, and 24 h after a single-dose oxazepam vs placebo administration in a crossover design [36].
• In this rapid, sensitive method for simultaneously determining diazepam and its biologically active metabolites--nordiazepam, oxazepam, and temazepam--in serum, 250 to 1000 microL of serum is extracted with ether and the extracted compounds are quantified by "high-performance" liquid chromatography on a Shimpack FLC-C8 microparticulate column [37].
• Determination of intact oxazepam by electron capture gas chromatography after an extractive alkylation reaction [38].

References