Temazepam Research Articles

Development and preliminary application of high-performance liquid chromatographic assay of urinary metabolites of diazepam in humans.

A simple high-performance liquid chromatographic method for the measurement of diazepam (DZP) and its major metabolites, N-desmethyldiazepam (DMDZP), temazepam (TZP) and oxazepam (OZP) in urine was developed. Preliminary studies of DZP metabolism were also undertaken in four healthy volunteers after administration of a single oral dose (4 mg) of DZP. The assay allowed the simultaneous determination of all analytes in 1 ml of urine and the detection limit was 2 ng/ml with a signal-to-noise ratio of 3. None of 22 drugs and 17 metabolites, except for mianserin, maprotiline and imipramine N-oxide, interfered with the detection of DZP metabolites. Recoveries of the analytes and the internal standard (prazepam) were > 82%. Intra- and inter-assay coefficients of variation for all analytes were < 5.5 and 4.1%, respectively. The mean (+/- S.D.) cumulative urinary excretions of DMDZP, TZP and OZP over 96 h after a single oral administration of DZP were 3.9 +/- 0.4, 6.6 +/- 1.4 and 2.8 +/- 0.6% of the dose, respectively. The urinary excretion of DZP was under the detection limit.

Substitution and racemization of 3‐hydroxy‐ and 3‐alkoxy‐1,4‐benzodiazepines in acidic aqueous solutions

AbstractOxazepam (OX), 3‐O‐methyloxazepam, 3‐O‐ethyloxazepam, temazepam (TMZ), 3‐O‐methyltemazepam, and 3‐O‐ethyltemazepam underwent acid‐catalyzed nucleophilic substitution reaction (hydrolysis) in an acetonitrile–oxygen‐18 water mixture to form either OX or TMZ in which the 3‐hydroxyl group was either partially or fully labeled with an oxygen‐18 atom. The dependence of the hydrolysis rates on solvent composition, temperature, ionic strength, and in deuterated solvent was studied by reversed‐phase high‐performance liquid chromatography (HPLC). The rates of racemization of enantiomeric compounds in acidic aqueous solutions were studied by both spectropolarimetry and chiral stationary phase HPLC. In acetonitrile: 2.5 M H2SO4 (4:1, v/v) at 50°C, enantiomers of OX and TMZ underwent racemization at rates ≥40‐fold faster than the rates of hydrolysis. Enantiomeric 3‐O‐alkyl derivatives of OX and TMZ in acidic aqueous solutions did not themselves undergo racemization and it was their hydrolysis products (either OX or TMZ) that underwent racemization. © 1995 Wiley‐Liss, Inc.

Temazepam does not interact significantly with erythromycin

Temazepam does not interact significantly with erythromycin

Hydrolysis of Temazepam in Simulated Gastric Fluid and Its Pharmacological Consequence

Temazepam (TMZ), a hypnotic and anxiolytic drug, underwent hydrolysis in simulated gastric fluid (SGF; pH 1.2). The hydrolysis reaction of TMZ in acetonitrile:SGF (1:19, v/v) at 37 °C was an apparent first‐order reaction, with a half‐life of 5.47 ± 0.17 h (i.e., ∼ 12% of the remaining TMZ was hydrolyzed per hour). The predominant hydrolysis product (2′‐benzoyl‐4′‐chloro‐N‐methyl‐2‐amino‐2‐hydroxyacetanilide) and a minor hydrolysis product [2‐(methylamino)‐5‐chlorobenzophenone], derived from acid‐catalyzed reaction of TMZ in an aqueous solution, were characterized by ultraviolet–visible absorption mass, infrared, and proton nuclear magnetic resonance spectra analyses. The kinetics of the hydrolysis reaction were studied as a function of acid concentration, temperature, and ionic strength and in deuterated solvent. Results indicated that the predominant hydrolysis reaction at pH ≈ pKa(1.46) was caused by protonation at N4, followed by a nucleophilic attack by water at C5 of the C5–N4 iminium ion and a subsequent ring‐opening reaction. Pharmacological activity tests in mice indicated that the predominant hydrolysis product of TMZ was inactive. The results suggest that a fraction of an orally taken TMZ may be inactivated by hydrolysis in the highly acidic gastric fluid.

A plea for further action on ???abuse resistant??? temazepam

A plea for further action on ???abuse resistant??? temazepam

Temazepam see Lorazepam/temazepam

Temazepam see Lorazepam/temazepam

Temazepam abuse causes concern

Temazepam abuse causes concern

In vitro drug metabolism and pharmacokinetics of Diazepam in cynomolgus monkey hepatocytes during culture for six days

Diazepam (DZ), N-desmethyl diazepam (NOR) and temazepam (TEM) were used as substrates in drug metabolism studies to characterize the changes in cytochrome P-450 mono-oxygenase pathways in hepatocytes isolated from cynomolgus monkeys, during culture for 6 days. Hepatocytes were incubated with DZ (20 μM), NOR (6 μM) or TEM (20 μM) for 3 hr at 3, 24, 48, 96 and 144 hr post-isolation in culture, and the profiles of disappearance of DZ, as substrate, and appearance of its metabolites determined. Major metabolites were NOR, TEM and oxazepam (OX). The kinetic profiles for the disappearance of DZ and the accumulation of metabolite were analysed using a four-compartment model and constants for the rates of formation of the metabolites were derived. There were significant changes during the period in culture for the rate constants of DZ demethylation, but no alteration in the 3-hydroxylation activities. Rates of DZ metabolism were unchanged during the initial 2 days in culture and well maintained for the subsequent 4 days, despite a fall in total cytochrome P-450 to 23% of initial values after 6 days. Cynomolgus monkey hepatocytes produce similar metabolite profiles for DZ to those found in man, both in vitro and in vivo, indicating that cynomolgus monkey hepatocytes may represent a relatively stable and valuable model of human drug metabolism.

Comment: Temazepam and Diphenhydramine in Nursing Homes

Comment: Temazepam and Diphenhydramine in Nursing Homes

Misuse of temazepam: Reply from the manufacturer

Misuse of temazepam: Reply from the manufacturer

Midazolam and Temazepam are Effective Hypnotics

Midazolam and Temazepam are Effective Hypnotics

Cognitive functioning in a hypnotic drug trial

AbstractIn a 2 week comparative trial between lormetazepam (LMA) and temazepam (TEM) in 162 insomniac patients, Critical Flicker Fusion Threshhold (CFFT) and Digit Symbol Substitution (DSS) tests were performed, pre‐treatment and at days 7 and 14. With neither drug was there any difference in CFFT, but highly significant improvement in DSS (p &lt; 0.001). Patients completed daily visual analogue scales concerned with various sleep parameters and daytime effects. Sleep was significantly improved with both drugs from day 1 onwards, as were daytime general wellbeing and alertness. There was significant improvement in daytime balance and coordination in the LMA group (p &lt; 0·001 by day 14) but not in the TEM group. Daytime anxiety improved significantly in both groups, but on day 14 this improvement was still significant in the LMA group (p &lt; 0·001) but not in the TEM group. The incidence of daytime fatigue (p &lt; 0·001), drowsiness (p &lt; 0·02) and headache (p &lt; 0·001) were significantly reduced with LMA and daytime fatigue (p &lt; 0·01) and headache (p &lt; 0·001) with TEM, but with no significant between group differences. The severity of daytime fatigue was significantly less with LMA than with TEM (p &lt; 0·05).

The safety of temazepam in overdose

The safety of temazepam in overdose

Pharmacodynamic evaluation of the benzodiazepine-oral contraceptive interaction.

The sedative, psychomotor, and memory effects of single oral doses of alprazolam (ALP), lorazepam (LOR), temazepam (TMP), and triazolam (TRZ) were evaluated in women taking oral contraceptives (OCs) and a comparable group of control women. Nine women taking OCs and 11 control women took doses of 1 mg ALP and 2 mg LOR and 10 OC users and 10 control women took 30 mg TMP and 0.5 mg TRZ on two occasions separated by 28 days. Minimal psychomotor impairment was noted after TMP. ALP, LOR, and TRZ produced greater performance impairment in the OC users. Correcting the maximum observed performance decrement for plasma concentration did not account for the differences between OC users and controls. After TMP, there was less sedation during the first 2 hours in OC users, who also had higher plasma TMP clearance. There were no differences in sedation between OC users and controls after ALP, LOR, and TRZ; however, there was less than 50% power to detect a 30% difference. Amnestic effects in OC users and controls did not differ after any of the four drugs. The observed patterns of anterograde amnesia were different, with the earliest and most pronounced recognition failure after TRZ (50% at 1.5 hours), while the LOR effect increased to a maximum (30%) 4 hours after dosing. Our data suggest that differences in benzodiazepine pharmacokinetics between OC users and control women do not account for observed differences in psychomotor impairment. Women taking OCs are more sensitive to the psychomotor effects of single oral doses of benzodiazepines.(ABSTRACT TRUNCATED AT 250 WORDS)

Zopiclone: this non-benzodiazepine hypnotic compares well with temazepam

Zopiclone: this non-benzodiazepine hypnotic compares well with temazepam

Effect of oral contraceptives on triazolam, temazepam, alprazolam, and lorazepam kinetics.

The effects of low-dose estrogen oral contraceptives (OC) on the elimination of the oxidized benzodiazepines triazolam (TRZ) and alprazolam (ALP) and the conjugated benzodiazepines temazepam (TMZ) and lorazepam (LOR) were studied in two parallel crossover studies of 20 women each. Women taking OC steroids containing low doses of estrogen and women matched for age, weight, and cigarette smoking received single oral doses of TRZ (0.5 mg) and TMZ (30 mg) or ALP (1 mg) and LOR (2 mg). Kinetics were determined as plasma concentrations during 48 hr after dosing. OCs inhibited the metabolism of ALP: The AUC increased and the elimination rate constant was greater in users of OCs. For TRZ, which has an intermediate extraction ratio, the AUC was increased by OCs but not significantly so. In contrast, OCs decreased the AUC for TMZ and the elimination rate constants for LOR and TMZ. The AUC of LOR was not affected by OCs. Low-dose estrogen OCs may therefore inhibit the metabolism of some oxidized benzodiazepines and accelerate the metabolism of some conjugated benzodiazepines.

Temazepam Leaves Volunteers Feeling Brighter than Nitrazepam

Temazepam Leaves Volunteers Feeling Brighter than Nitrazepam

Chronic Toxicity/Carcinogenesis Study of Temazepam in Mice and Rats

Chronic Toxicity/Carcinogenesis Study of Temazepam in Mice and Rats