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At least 19 recordsLinked to original sources
PubMed1981

Effect of temazepam and temazepam-ethanol on sleep.

The effects of temazepam 20 mg and temazepam 20 mg plus whisky 100 ml on sleep and performance were investigated in 5 healthy volunteers in comparison with placebo. In the sleep laboratory, after temazepam there was a trend for reduction of sleep latency, stage wake and stage 1 sleep, and for an increase in REM sleep. The addition of alcohol to the regimen reduced the sleep latency still further, and diminished REM sleep. In subjective assessments, temazepam received the highest score for quality of sleep and the temazepam/alcohol combination that for ease of falling asleep. None of the observed changes reached statistical significance. No morning hangover, as measured by effects on wakefulness, performance or affective state, was seen after the combined treatment. Its effect on blood pressure was negligible. It is concluded that the combined administration of temazepam and alcohol in the doses used here does not result in excessive additive, but in moderate pharmacological effects.

Adult↗
PubMed1991

Determination of temazepam and temazepam glucuronide by reversed-phase high-performance liquid chromatography.

A rapid and sensitive method for extracting temazepam from human serum and urine is presented. Free temazepam is extracted from plasma and urine samples using n-butyl chloride with nitrazepam as the internal standard. Temazepam glucuronide is analyzed as free temazepam after incubating extracts with beta-glucuronidase. Separation is achieved using a C8 reversed-phase column with a methanol-water-phosphate buffer mobile phase. An ultraviolet detector operated at 230 nm is used and a linear response is observed from 20 ng/ml to 10 micrograms/ml. The limit of detection is 15.5 ng/ml and the limit of quantitation is 46.5 ng/ml. Coefficients of variation are less than 10% for concentrations greater than 50 ng/ml. Application of the methodology is demonstrated in a pharmacokinetic study using eight healthy male subjects.

Chromatography, High Pressure Liquid↗
PubMed1991

A comparison of the hypnotic effects of temazepam capsules and temazepam elixir.

The effect of temazepam as a hypnotic was assessed with two different formulations, the solution-filled soft gelatin capsule and the more recently introduced elixir. Sixty psychiatric in-patients were included in the trial and 59 completed it. The study followed a double-blind crossover design for two consecutive nights. Patients took a capsule and elixir each night, but only one would contain the active ingredient (in a dose of 20 mg temazepam). In contrast to earlier work with volunteers, the elixir failed to reveal more of the characteristics of an ideal hypnotic. In fact, in those measures that were statistically significant, the balance favoured the capsule. We conclude that although there are many situations where an elixir is clearly clinically preferable, the essential hypnotic effect of the elixir is not conspicuously different to that of the capsule.

Adolescent↗
PubMed1994

Effects of intravenous temazepam. I. Saccadic eye movements and electroencephalogram after fast and slow infusion to pseudo steady state.

OBJECTIVE: To study the pharmacodynamic effects of intravenous temazepam after different infusion rates to pseudo steady-state concentrations. METHODS: This was a randomized, double-blind, placebo-controlled crossover study in an academic department of clinical pharmacology. Subjects were nine healthy volunteers. A computerized infusion pump was used to obtain target plasma concentrations of temazepam after 30 or 120 minutes and to maintain these levels for 2 hours. A vehicle infusion, similar to the 30-minute (fast) infusion was used as a placebo control. Infusion schedules were based on data obtained from individual subjects after infusion of 0.4 mg/kg temazepam in 30 minutes. Target plasma concentrations were chosen to induce subhypnotic effects and averaged (+/- SD) 597 +/- 123 ng/ml. Venous plasma concentrations of temazepam were measured by HPLC. Free fractions of temazepam were assessed at the start of the pseudo steady-state concentration intervals. Electroencephalogram alpha and beta amplitudes, saccadic peak velocity, and saccadic latency were used as pharmacodynamic parameters. RESULTS: The rate of change of plasma concentrations averaged 21 +/- 4 ng/ml.min-1 during fast infusion and 5 +/- 1 ng/ml.min-1 during slow infusion of temazepam. Average pseudo steady-state concentrations were 639 +/- 132 ng/ml after fast infusion and 629 +/- 133 ng/ml after slow infusion. At the onset of pseudo steady-state concentration intervals the average free fractions of temazepam were 44% (95% confidence interval, 19% to 61%) lower for slow than for fast infusions. Compared with the slow infusion, electroencephalogram beta amplitudes were significantly larger during the first 30 minutes of pseudo steady-state concentration after fast infusion of temazepam. No significant differences were found for the other parameters. There was a slight decline of temazepam effects during the pseudo steady-state concentration intervals for all parameters after the fast infusion and for saccadic peak velocity and saccadic latency after the slow infusion. CONCLUSIONS: The pharmacodynamic effects of intravenous temazepam may depend partly on the rate of administration. Differences in pharmacodynamic effects after fast and slow infusions could be caused by changes in protein binding over time.

Dose-Response Relationship, Drug↗
PubMed1993

A comparison of the acute behavioral effects of triazolam and temazepam in normal volunteers.

Two experiments were conducted to assess the acute behavioral effects of triazolam and temazepam in healthy, non-drug abusing men in double-blind, placebo-controlled, crossover trials, where all subjects received all possible doses. These drugs were compared to examine allegations that triazolam produces greater behavioral impairment than temazepam. Drug effects were assessed during 4-h sessions using measures of recall, learning, psychomotor performance, and subject ratings assessing drug effects and abuse potential. In experiment 1, triazolam (0.25 and 0.5 mg/70 kg) produced greater behavioral impairment than temazepam (15 and 30 mg/70 kg). However, triazolam also produced greater increases than temazepam in subject ratings of drug strength, drunkenness and sleepiness, suggesting the dose ranges compared may not have been clinically equivalent. Experiment 2 was conducted to assess whether a higher dose of temazepam than tested in experiment 1 would produce levels of behavioral impairment comparable to those observed with triazolam in experiment 1. In experiment 2, the temazepam dose was increased to 60 mg/70 kg while the triazolam dose was 0.5 mg/70 kg which was the highest dose tested in experiment 1. These doses produced comparable increases in subject ratings of drug strength, drunkenness and sleepiness, but temazepam produced significantly more behavioral disruption than triazolam. These findings do not support the position that triazolam produces greater behavioral impairment than temazepam, and may even suggest that across a wide range of doses triazolam is less disruptive than temazepam.

Adult↗
PubMed1985

Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics.

The kinetics of temazepam, 30 mg, were evaluated in 11 patients with end-stage renal disease. Age ranged from 18 to 65 years. On two occasions separated by 1 week, single oral 30 mg doses of temazepam were given once with water (TM) and once with 3600 mg aluminum hydroxide gel (TM + AHG). There were no significant differences in the maximum plasma concentration, the time to reach maximum concentration, or elimination rates between TM and TM + AHG dosing. In approximately half the subjects there were secondary temazepam peak concentrations. In the remaining subjects, temazepam elimination was biphasic, with the terminal t1/2 ranging from 11 to 77 hours. There was a lag time before absorption in all subjects. The percent free temazepam in plasma from dialysis subjects ranged from 4.4% to 8.8% (mean = 5.9%). Compared with literature reports of subjects with normal renal function, the maximum plasma concentration was lower and the percent free temazepam was higher in dialysis subjects. When sedation score was plotted against plasma temazepam concentration, there was clockwise hysteresis consistent with tolerance or adaptation to effects of the drug. Thus aluminum hydroxide gel does not affect temazepam absorption. The clinical significance of the low plasma concentrations and high free temazepam fraction in dialysis subjects is uncertain.

Absorption↗
PubMed1990

Effect of temazepam on blood pressure regulation in healthy elderly subjects.

1. Blood pressure regulation was studied in 12 healthy elderly subjects after double-blind randomised administration of placebo, 15 mg and 30 mg temazepam at 10.00 h and 22.00 h. 2. Supine and standing heart rate and blood pressure were measured after daytime administration and supine measurements were obtained during sleep. 3. Temazepam caused a fall in systolic blood pressure and an increase in heart rate after morning administration. These changes were greater in the standing position and were dose-dependent; for standing blood pressure and heart rate 1 h after administration there was a 7 mm Hg fall and 6 beats min-1 increase after 15 mg temazepam and a 10 mm Hg fall and 8 beats min-1 increase after 30 mg temazepam. Temazepam magnified the fall in systolic blood pressure and increase in heart rate that occurred with standing. Temazepam enhanced the fall in systolic blood pressure that occurred during sleep (mean +/- s.d.; placebo: -23 +/- 10 mm Hg, 15 mg temazepam: -31 +/- 13 mm Hg, 30 mg temazepam: -36 +/- 14 mm Hg). 4. These changes in blood pressure regulation caused by temazepam may have clinical importance in some elderly individuals.

Aged↗
PubMedDate not supplied

Oxidative versus conjugative biotransformation of temazepam.

Twenty-four healthy volunteers, aged 21-59 years, received single 30 mg oral doses of the benzodiazepine hypnotic temazepam. Levels of intact temazepam were determined in multiple plasma samples drawn during 48 h after dosage. Intact temazepam, its direct glucuronide conjugate, and the conjugate of its demethylated (oxidized) metabolite oxazepam were measured in two consecutive 24-h urine collections. Mean kinetic variables for temazepam in plasma were: peak plasma level (Cmax), 873 ng ml-1; time of peak, 1.36 h after dosage; volume of distribution, 0.961 kg-1; elimination half-life 9.9 h; clearance, 1.16 ml min-1 kg-1. Volume of distribution increased significantly with body weight (r = 0.67, p less than 0.001), and Cmax decreased with weight (r = -0.58, p less than 0.01). Only 0.2 per cent of the dose was excreted as intact temazepam, and negligible amounts as intact oxazepam. However, 39 per cent of the dose was recovered as temazepam glucuronide, and oxazepam glucuronide accounted for another 4.7 per cent of the dose. The remainder was not accounted for. Thus, a significant fraction of temazepam clearance occurs by direct glucuronide conjugation, with the conjugate temazepam glucuronide excreted in urine. A much smaller fraction undergoes parallel oxidation to form oxazepam, which is subsequently conjugated to oxazepam glucuronide and excreted in urine.

Adult↗
PubMedDate not supplied

Evaluation of temazepam as a hypnotic.

Temazepam is a 1,4-benzodiazepine, newly marketed in the United States for the symptomatic treatment of the complaint of insomnia. The manufacturer recommends a dose of 30 mg before bedtime for most adults and 15 mg for geriatric or debilitated patients. A dose of 30 mg usually produces peak plasma concentrations within 3 hours after oral ingestion and has a mean half-life of 10 to 15 hours. Thus, temazepam is absorbed more slowly and metabolized more quickly than flurazepam, the only other benzodiazepine marketed in the United States specifically for insomnia. Eight sleep laboratory and 21 clinical studies on temazepam indicate that temazepam reduces awakening during the night and increases sleep duration. However, there was no consistent evidence that temazepam reduces sleep latency--probably because temazepam, taken at bedtime, does not reach sufficiently high blood levels in time to affect sleep onset. One sleep laboratory study on 8 insomniac patients given 35 consecutive nightly doses of 30 mg found no evidence of tolerance or rebound insomnia. Studies on tolerance, metabolism and carry-over effects have shown that temazepam has no long-acting metabolites and does not affect waking function following use at bedtime. In patients for whom hypnotic medication is appropriate, temazepam should be an effective drug for reducing most symptoms of insomnia.

Anti-Anxiety Agents↗
PubMed1981

Effect of age and gender on disposition of temazepam.

Thirty-two male and female volunteers, 24-84 years of age, ingested single 30-mg doses of temazepam, a 3-hydroxy-1,4-benzodiazepine derivative used as a hypnotic agent. Kinetics of total and unbound temazepam were determined from multiple plasma temazepam concentrations measured during 48 hr after the dose. The temazepam elimination half-life ranged from 8 to 38 hr and was longer in women than in men (16.8 versus 12.3 hr, p less than 0.05). Likewise, clearance of total temazepam (assuming complete absorption) was higher in men than in women (1.35 versus 1.02 ml/min/kg, p less than 0.025). Neither half-life nor clearance was significantly related to age. The volume of distribution of total temazepam (mean 1.40 liters/kg) was unrelated to age or gender. Temazepam was extensively protein bound, with a mean free fraction of 2.6% (range 12.7-3.4%). The free fraction increased with age (r = 0.45, p = 0.01), partly due to the inverse relation of the free fraction to plasma albumin concentration (r = -0.34, p = 0.06) and the age-related decline in plasma albumin (r = -0.49, p less than 0.005). After correction for individual differences in binding, clearance of unbound temazepam in men was higher than in women (50.5 versus 39.7 ml/min/kg, 0.05 less than p less than 0.01), and it tended to decline with age in both sexes (r = -0.44 and -0.43, respectively, p = 0.1).

Adult↗
PubMed1988

Aging: changes in a passive-avoidance response with brain levels of temazepam.

Acute intravenous (IV) injections of temazepam were examined for the ability to impair the performance of young (3-4-month-old), mature (12-15-month-old) and old (28-30-month-old) male Fischer 344 rats in the step-down task relative to vehicle-injected controls. The effect of temazepam on the passive-avoidance response could be characterized as a U-shaped function of age. The performance of the mature rat was not significantly impaired by an IV injection of temazepam between 18 and 320 micrograms/kg. Temazepam was more effective in impairing the performance of the young and old rat. The brain levels of temazepam after a single IV injection of 18 micrograms/kg in mature and senescent rats, and 32 micrograms/kg in young rats were measured over a 2-hour time period. The brain of the mature rat was exposed to less temazepam between 0 and 120 minutes than the brain of the old rat. Therefore, the increased sensitivity of the senescent rat relative to the mature rat may in part be due to changes in the pharmacokinetics of temazepam. However, the inability of temazepam (between 18 and 320 micrograms/kg) to impair the performance of mature rats in the passive-avoidance task suggests that pharmacodynamic changes may be involved in the decreased sensitivity of mature rats relative to young and senescent rats.

Aging↗
PubMed1993

Benzodiazepines in congestive heart failure: effects of temazepam on arousability and Cheyne-Stokes respiration.

We studied seven male patients with moderate to severe congestive heart failure (CHF) [left ventricular ejection fraction (LVEF) = 22.4 +/- 6.7; mean +/- SD] in a double-blind crossover trial to determine the effects of temazepam 15 mg on arousability, sleep architecture, Cheyne-Stokes respiration (CSR) and nighttime oxygen saturation. Sleep architecture was not markedly improved with temazepam. There was no significant change in total sleep time (TST) (383.1 +/- 14.1 minutes to 396.6 +/- 15.4 minutes, p = ns) (mean +/- SE, placebo vs. temazepam) or total wake time (TWT) (96.9 +/- 14.0 vs. 81.4 +/- 14.0 minutes, p = ns). Sleep stage proportions did not change appreciably except for a reduction in stage 1 sleep (6.7 +/- 1.2% vs. 4.0 +/- 1.0%, p < 0.05). Microarousals per hour of sleep decreased with temazepam (21.1 +/- 2.7/hour vs. 13.9 +/- 2.1/hour placebo, p < 0.05), with the largest change occurring in stage 2 (24.9 +/- 5.4/hour vs. 15.0 +/- 3.1/hour, p < 0.05). Wake time during sleep (WDS) was reduced from 82.5 +/- 11.7 minutes to 54.5 +/- 9.4 minutes, p < 0.03. Daytime alertness was improved with temazepam as was indicated by an increase in mean latency to sleep [multiple sleep latency test (MSLT) = 7.1 +/- 2.4 vs. 5.7 +/- 2.0 minutes, p < 0.04) on days following treatment with temazepam. There was no significant change in CSR as a percentage of TST (38.7 +/- 13.6% vs. 32.5 +/- 11.8%, p = ns). However, the apnea/hypopnea index (AHI) (10% filter) was decreased in stage 1 (28.1 +/- 9.7/hour vs. 15.6 +/- 8.2/hour). Overnight oxygen saturation did not change with temazepam (95.1 +/- 0.6% both nights) and the percentage of TST spent below 90% oxygen saturation was minimal for both conditions (1.5 +/- 1.1% vs. 2.2 +/- 1.7%, p = ns). We conclude that CHF patients with CSR experience frequent arousals and that these arousals can be reduced with temazepam. There was an improvement in daytime somnolence. There was no worsening of nighttime oxygen saturation.

Aged↗
PubMed1990

A double-blind placebo-controlled trial of zopiclone 7.5 mg and temazepam 20 mg in insomnia.

Zopiclone, a cyclopyrrolone with hypnotic properties was compared with temazepam and placebo in the treatment of insomnia. After a week's washout period, suitable subjects were allocated at random to zopiclone 7.5 mg or temazepam 20 mg or placebo for 2 weeks. Measurements of psychomotor function using the Leed's psychomotor tester and letter cancellation were carried out on day 0, 7 and 14. Sleep latency, duration of sleep and number of times waking during the night were recorded on a sleep diary filled by the subjects nightly. Forty-four subjects completed the trial, 15 taking zopiclone, 16 taking temazepam and 10 taking placebo. Both zopiclone and temazepam had significant hypnotic properties when compared to placebo. Zopiclone increased total sleep time in both weeks of the trial while temazepam increased sleep time in the first week only. There was no significant deterioration in psychomotor performance at the end of both weeks for zopiclone. Critical flicker fusion was significantly increased in subjects on temazepam. There were no abnormalities for both zopiclone and temazepam subjects in the blood picture, renal profile, liver function, urine and ECG before and after the study. Zopiclone is an effective hypnotic comparable to temazepam.

Adult↗
PubMed1986

Pharmaco-EEG, behavioural methods and blood levels in the comparison of temazepam and flunitrazepam.

In a double-blind placebo-controlled cross-over study, the blood levels and pharmacodynamic properties of temazepam were compared with flunitrazepam using quantitative pharmaco-EEG and psychometric methods in ten healthy volunteers. Computer-assisted spectral analysis of the EEG after three doses of temazepam (10 mg, 20 mg and 40 mg) compared with placebo showed statistically significant changes in brain function. These changes were also seen after the administration of the reference drug (flunitrazepam 2 mg) and are typical of anxiolytic sedatives. Psychometric and psychophysiological tests demonstrated significant alterations at the behavioural level, especially after higher doses of temazepam and 2 mg flunitrazepam, as expected. However, low doses or low blood levels of temazepam induced an improvement of performance in certain variables. Dose-efficacy calculations identified 2 mg flunitrazepam and 40 mg temazepam as the most CNS-effective, followed by 20 mg and 10 mg temazepam, while the least changes occurred after placebo. Time-efficacy calculations showed marked inter-drug differences. The pharmacodynamics of both drugs parallel their respective pharmacokinetics. Regression and correlation analyses between blood levels and EEG or psychometric changes revealed that beta activity and the centroid of the EEG were positively correlated with plasma levels, while alpha activity, psychometric variables and skin conductance were negatively correlated. Psychometric variables started to deteriorate above a blood level of approximately 250 ng/ml, while below this level an improvement was seen. Such (sedative) blood levels were only reached after doses higher than 10 mg temazepam. Our findings indicate that 10 mg temazepam has tranquilizing properties, while 20 mg and 40 mg doses exert, in addition, sedative sleep-inducing effects.

Administration, Oral↗
PubMed1991

Effects of temazepam on sleep, performance, and rhythmic 6-sulphatoxymelatonin and cortisol excretion after transmeridian travel.

The effects of 20-mg doses of the short-acting benzodiazepine, temazepam, on sleep, performance and pineal, adrenal and temperature rhythms were investigated in a placebo-controlled, double-blind crossover study. Ten healthy males were studied 4 d prior to flying from Sydney to London via Tokyo and Anchorage (11 time zones). Temazepam or placebo were administered at 2300 hours (local time) during the flight and for 4 d after arrival. After a 7-d recreation break in London, the subjects returned to Sydney via Moscow and Tokyo and again took five doses of temazepam or placebo. During the 5 d following their arrival in London or Sydney, the subjects collected urine, had rectal temperature monitored, performed a battery of performance tests and filled out questionnaires. Temazepam significantly improved various subjective sleep characteristics, particularly on the first few nights. Performance (choice reaction time, critical flicker fusion threshold and pencil and paper tests) was not impaired by temazepam treatment. The pineal rhythm was assessed by urinary 6-sulphatoxymelatonin excretion rate determinations. The time of peak 6-sulphatoxymelatonin excretion (acrophase) occurred progressively later each day after arrival in London and Sydney, however the rate of adjustment of the rhythm was not affected by temazepam. Similarly, the urinary cortisol and temperature rhythms adjusted to the new environments by progressive delay with no drug effect being evident. Administration of temazepam clearly had a beneficial effect on sleep and alertness following transmeridian travel, without detrimental effects on performance. There was no evidence to suggest that temazepam altered the rates of entrainment of physiological rhythms to the new environments.

Adult↗
PubMed1986

Temazepam clearance unaltered in cirrhosis.

The kinetics of a single oral dose of the benzodiazepine hypnotic temazepam was evaluated in nine patients with biopsy-proven cirrhosis and in seven healthy controls matched for age and sex. Peak serum temazepam concentrations were reached later in cirrhotics than in controls (2.9 versus 0.6 h after dosage; p less than 0.05), indicating slower temazepam absorption in patients with cirrhosis. Temazepam volume of distribution was smaller in cirrhotics compared to controls, and elimination half-life shorter (10.6 versus 14.6 h). However, these differences were not significant. There were no significant differences between cirrhotics and controls in clearance of total temazepam (1.03 versus 1.03 ml/min/kg), clearance of unbound temazepam (27 versus 31 ml/min/kg), or free fraction in serum (3.9 versus 3.5% unbound). In two cirrhotic patients who received 20 mg of temazepam daily for 8 days, the extent of accumulation was consistent with the dosage interval relative to the elimination half-life, and was similar to the accumulation profile in healthy volunteers. Thus the onset of temazepam hypnotic activity may be delayed in cirrhotic patients, but the rate of elimination and the extent of accumulation are not altered compared to healthy persons of similar age and sex.

Administration, Oral↗
PubMed1984

Noninteraction of temazepam and cimetidine.

The possible kinetic interaction of the hypnotic temazepam and the H2-receptor antagonist cimetidine was evaluated. Nine healthy male and female volunteers received a 30-mg oral dose of temazepam on two occasions in random sequence, separated by at least 1 week. On one occasion, temazepam was given in the otherwise drug-free state; on the other, temazepam was given with concurrent administration of cimetidine, 300 mg every 6 h. Mean pharmacokinetic parameters for temazepam in control versus cimetidine trials were: peak plasma concentration, 560 versus 498 ng/mL; time of peak concentration, 2.0 versus 2.1 h after the dose; volume of distribution, 1.30 versus 1.39 L/kg; elimination half-life, 9.9 versus 11.4 h; total clearance, 1.59 versus 1.60 mL/min/kg; free fraction of temazepam in plasma, 4.1 versus 3.8% unbound. Cimetidine has been shown to reduce the metabolic clearance of the benzodiazepines that are biotransformed by oxidative mechanisms. Temazepam, transformed by conjugation, appears unaffected by the coadministration of cimetidine.

Adult↗
PubMed1994

Lack of interaction of erythromycin with temazepam.

Erythromycin is a strong inhibitor of cytochrome P450 [CYP3A4] and has a potentially dangerous interaction with midazolam and triazolam. The possible interaction between erythromycin and a short-acting benzodiazepine, temazepam, was investigated in a double-blind, randomized crossover study. Ten healthy volunteers received 500 mg erythromycin or placebo orally three times a day for 6 days followed by a challenge dose of 20 mg temazepam. Plasma samples were collected for the determination of temazepam, oxazepam, and erythromycin, and psychomotor effects were measured during the 24 h after intake of temazepam. Erythromycin did not change the pharmacokinetics or pharmacodynamics of temazepam to a statistically significant degree. The metabolic fate of temazepam and its almost complete bioavailability explain the lack of interaction. Temazepam, unlike midazolam or triazolam, can thus be prescribed in the usual doses for patients receiving erythromycin.

Administration, Oral↗