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Experimental and Clinical... Feb 2010The present study compared the acute dose effects of the benzodiazepine triazolam and the anticholinergic scopolamine on metamemory (knowledge and awareness of one's own... (Comparative Study)
Comparative Study Randomized Controlled Trial
The present study compared the acute dose effects of the benzodiazepine triazolam and the anticholinergic scopolamine on metamemory (knowledge and awareness of one's own memory) in a two-phase paradigm designed to assess effects on both monitoring and control components of metamemory in both semantic (general knowledge) and episodic memory (cued-recall) tasks. Placebo and 2 doses each of triazolam (0.125, 0.25 mg/70 kg, oral) and scopolamine (0.25, 0.50 mg/70 kg, subcutaneous) were administered to 80 healthy volunteers (16 per group) in a double-blind, double-dummy, independent groups design. Both triazolam and scopolamine impaired episodic memory (quantity and accuracy) but not semantic memory. Results suggested that both drugs impaired monitoring as reflected in absolute accuracy measures (impaired calibration in the direction of overconfidence) and control sensitivity (the relationship between confidence and behavior). Overall, the results did not provide evidence for differences between triazolam and scopolamine in memory or metamemory. In addition to the clinical relevance of the observed effects, this study adds to the accumulating body of cognitive psychopharmacological research illustrating the usefulness of drug-induced amnesia as a vehicle to explore memory and metamemory.
Topics: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory; Mental Recall; Psychomotor Performance; Scopolamine; Triazolam; Young Adult
PubMed: 20158291
DOI: 10.1037/a0018061 -
RSC Advances Sep 2022The combined abuse of benzodiazepines and antipsychotics has become a global problem, and to develop a highly sensitive and selective method for monitoring of...
The combined abuse of benzodiazepines and antipsychotics has become a global problem, and to develop a highly sensitive and selective method for monitoring of benzodiazepine hypnotics and antipsychotics is urgently necessary. In this work, we established a rapid method for the simultaneous determination of benzodiazepines (diazepam, alprazolam, triazolam, and estazolam) and antipsychotic drugs (clozapine, and chlorpromazine) based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), specificity, matrix effect and carry-over effect were verified in detail. The results of the recovery and repeat experiments proved that the proposed UPLC-MS method possessed very satisfactory accuracy and precision. The LOD and LOQ of the six psychoactive substances were as low as 0.001-0.005 and 0.005-0.01 μg L, respectively. The proposed method was employed to analyze urine samples which were pretreated with a protein precipitation process. The potential influences of precipitants on the analysis results were evaluated statistically, and 0.1% formic acid/acetonitrile/water was selected as the optimum precipitation agent. The detection of the targets was free from matrix and carryover effects.
PubMed: 36320845
DOI: 10.1039/d2ra04869h -
Canadian Medical Association Journal Aug 1983
Topics: Adult; Alcoholism; Anti-Anxiety Agents; Humans; Male; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Triazolam
PubMed: 6135500
DOI: No ID Found -
Psychopharmacology Sep 2009Illicit gamma-hydroxybutyrate (GHB) has received attention as a "date rape drug" that produces robust amnesia; however, there is little experimental evidence in support... (Comparative Study)
Comparative Study
RATIONALE
Illicit gamma-hydroxybutyrate (GHB) has received attention as a "date rape drug" that produces robust amnesia; however, there is little experimental evidence in support of GHB's amnestic effects.
OBJECTIVES
This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers.
MATERIALS AND METHODS
Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined.
RESULTS
Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate.
CONCLUSIONS
Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers.
Topics: Adult; Cognition; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory, Short-Term; Mental Recall; Middle Aged; Neuropsychological Tests; Observation; Psychomotor Performance; Sodium Oxybate; Triazolam
PubMed: 19543883
DOI: 10.1007/s00213-009-1589-1 -
Dose-response : a Publication of... 2022Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in... (Review)
Review
Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.
PubMed: 36158743
DOI: 10.1177/15593258221120485 -
Yakugaku Zasshi : Journal of the... 2023The evaluation and prediction of pharmacokinetics in humans is important in the field of drug discovery and development. Generally, human pharmacokinetics is predicted... (Review)
Review
The evaluation and prediction of pharmacokinetics in humans is important in the field of drug discovery and development. Generally, human pharmacokinetics is predicted using physiologically based pharmacokinetic models that include physiological and physicochemical (drug) parameters obtained from in vitro assays. Specific organ dysfunction, such as liver disease, also affects the functions of other organs, causing unexpected pharmacokinetic fluctuations. I investigated the effect of cholestasis on intestinal drug absorption in mice subjected to bile duct ligation (BDL). The intestinal absorption and permeability of imatinib was decreased in BDL mice compared with sham-operated mice, and this may be attributed to the up-regulation of the efflux transporter, breast cancer resistance protein. However, a single-organ experimental system cannot predict such pharmacokinetic changes. To overcome this challenge, I investigated a microphysiological system (MPS) equipped with intestinal and hepatic cells for pharmacokinetic evaluation. The glucuronidation of triazolam was significantly increased in an enterohepatic MPS compared with a single-culture system. These results suggested that the elucidation of organ interactions requires the use of an MPS loaded with human cells in combination with laboratory animal studies. In this review, I present the results of my evaluation of organ interactions using animal models and MPSs in the Award for Young Scientists from the Pharmaceutical Society of Japan, Hokuriku Branch.
Topics: Animals; Humans; Mice; ATP Binding Cassette Transporter, Subfamily G, Member 2; Cholestasis; Intestines; Liver; Neoplasm Proteins; Pharmacokinetics; Enterohepatic Circulation
PubMed: 36724921
DOI: 10.1248/yakushi.22-00172 -
British Journal of Clinical Pharmacology Jan 1996A threefold higher area under the plasma drug concentration-time curve (AUC) of nifedipine, a substrate of cytochrome P4503A (CYP3A), has been shown in Southern Asians... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A threefold higher area under the plasma drug concentration-time curve (AUC) of nifedipine, a substrate of cytochrome P4503A (CYP3A), has been shown in Southern Asians when compared with Caucasians. To determine if these differences are specific to nifedipine or apply to other substrates of CYP3A, we examined the pharmacokinetics and pharmacodynamics of 0.375 mg triazolam, another substrate of CYP3A, in eight healthy Caucasians and eight healthy Southern Asians in a double-blind placebo-controlled study. When compared with Caucasians, Southern Asians achieved higher maximum plasma concentration (Cmax) (8.0 +/- 2.6 vs 4.8 +/- 1.9 ng ml-1; the 95% confidence interval (CI) of the mean difference was 0.76 to 5.7; P < 0.01) and had a shorter time to reach maximal concentration (tmax) (45 min (range 30-75) vs 90 min (range 60-145); the 95% CI of the mean difference was -69 to -20; P < 0.002). Triazolam AUC, clearance and partial metabolic clearance did not differ significantly between Southern Asians and Caucasians. Significant differences were found in postural sway after triazolam when compared with placebo in both Caucasians (double stance: eyes open (DSEO): 172.9 +/- 82.9 vs 1138.9 +/- 1182.4; the 95% CI of the mean difference was -1897.2 to -34.4; P < 0.04; and Southern Asians (DSEO: 216.2 +/- 80.9 vs 1086.0 +/- 827.1; the 95% CI of the mean difference was -1564.2 to -175.6; P = 0.02; double stance: eyes closed (DSEC): 207.5 +/- 89.8 vs 1156.9 +/- 932.1; the 95% CI of the mean difference was -1718.5 to -178.5; P = 0.02; with no significant difference between the two ethnic groups. These results suggest that the large inter-ethnic difference in nifedipine clearance are not generalizable to all CYP3A4 substrates.
Topics: Adult; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Double-Blind Method; Half-Life; Humans; Hypnotics and Sedatives; India; Male; Mixed Function Oxygenases; Postural Balance; Triazolam; United States; White People
PubMed: 8824695
DOI: 10.1111/j.1365-2125.1996.tb00160.x -
Korean Journal of Anesthesiology Jun 2017Benzodiazepines have been used preoperatively as part of an anesthesia regimen to attenuate the anxiety of patients. In this study, we aimed to examine the effect of...
BACKGROUND
Benzodiazepines have been used preoperatively as part of an anesthesia regimen to attenuate the anxiety of patients. In this study, we aimed to examine the effect of oral triazolam, a short-acting benzodiazepine, on anxiety, sedation, and amnesia.
METHODS
Ninety patients, aged 20-55 years, were randomly assigned to receive no premedication, or to receive triazolam 0.25 mg or 0.375 mg 1 h before anesthesia. Anxiety score, sedation score, blood pressure, heart rate and psychomotor performance were measured on the evening before surgery and on the day of surgery. Additional tests of psychomotor performance were performed in the postanesthesia care unit and on the next day of surgery. The occurrence of amnesia, bispectral index (BIS), recovery profiles and patient satisfaction with overall anesthesia care were also evaluated.
RESULTS
Changes in the anxiety and sedation scores on the day of surgery were not significantly different among groups, whereas the increases in systolic blood pressure and heart rate were significantly less in both triazolam groups. The triazolam groups both showed a higher incidence of high satisfaction scores (≥ 2). The two triazolam groups also showed similar outcomes, except for a dose-dependent increase in the number of patients with amnesia and BIS values < 90. Delayed recovery from general anesthesia and psychomotor impairment were not observed in the triazolam groups.
CONCLUSIONS
Triazolam 0.25 mg or 0.375 mg reduced the hemodynamic changes associated with anxiety, produced potent amnesia, and improved patient satisfaction. We suggest that triazolam can be used effectively as anesthetic premedication in adults.
PubMed: 28580079
DOI: 10.4097/kjae.2017.70.3.292 -
Drug and Alcohol Dependence Dec 1998The performance, observer-rated, and participant-rated effects of orally administered placebo, and two benzodiazepines, flunitrazepam (2, 4 and 8 mg/70 kg) and triazolam... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
The performance, observer-rated, and participant-rated effects of orally administered placebo, and two benzodiazepines, flunitrazepam (2, 4 and 8 mg/70 kg) and triazolam (0.25, 0.5 and 1 mg/70 kg), were compared in 14 sedative drug abusers using a double-blind crossover design. Both flunitrazepam and triazolam produced dose-related decrements in memory and psychomotor/cognitive performance, and increases in many participant- and observer-rated measures. Effects of flunitrazepam had an earlier onset and a longer duration than those of triazolam. Although there was evidence that the flunitrazepam doses selected for study were somewhat higher overall relative to the selected triazolam doses, analysis of the participant-rated measures collected 24 h after drug administration (next-day) suggests that flunitrazepam may have a greater abuse liability than triazolam when abuse liability is assessed 24 h after drug administration. The highest flunitrazepam dose produced effects that were significantly greater than those of the highest triazolam dose on next-day ratings of good effects, take again, and worth; all tested flunitrazepam doses produced effects greater than any triazolam dose on next-day ratings of liking and take again. The highest flunitrazepam dose, but no triazolam dose, significantly increased the maximum dollar value at which participants chose drug over money in a Drug versus Money Choice Procedure.
Topics: Adult; Anti-Anxiety Agents; Arousal; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Flunitrazepam; Humans; Hypnotics and Sedatives; Male; Mental Recall; Motivation; Neuropsychological Tests; Psychomotor Performance; Substance-Related Disorders; Triazolam
PubMed: 10933340
DOI: 10.1016/s0376-8716(98)00110-0 -
The New England Journal of Medicine Jun 1991Elderly persons frequently appear to be sensitive to the effects of many drugs that depress the central nervous system. We studied the effect of age on the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Elderly persons frequently appear to be sensitive to the effects of many drugs that depress the central nervous system. We studied the effect of age on the pharmacokinetics and pharmacodynamics of the benzodiazepine hypnotic agent triazolam, now the most frequently prescribed hypnotic drug in the United States.
METHODS
Twenty-six healthy young subjects (mean age, 30 years) and 21 healthy elderly subjects (mean age, 69 years) participated in a four-way crossover study. After a single-blind adaptation trial with placebo, each subject received, in random order and in double-blind fashion, single doses of placebo, 0.125 mg of triazolam, and 0.25 mg of triazolam. For 24 hours after the administration of each of the three study medications, plasma triazolam levels were determined and psychomotor performance, memory, and degree of sedation were assessed.
RESULTS
Plasma triazolam concentrations increased in proportion to the dose, but the elderly subjects had higher plasma concentrations due to reduced clearance of the drug. The degree of sedation as rated by an observer and the reduction in the subjects' performance on the digit-symbol substitution test were both greater in the elderly than in the young subjects after they were given the same doses. The relation of the plasma triazolam concentration to the degree of impairment was similar for the two groups. As part of the study, information was presented 1 1/2 hours after the administration of the drugs; the subjects' ability to recall the information 24 hours later was impaired by both doses of triazolam, and the percent decrease was similar in the young and elderly groups.
CONCLUSIONS
Triazolam caused a greater degree of sedation and greater impairment of psychomotor performance in healthy elderly persons than in young persons who received the same dose. These effects resulted from reduced clearance and higher plasma concentrations of triazolam rather than from an increased intrinsic sensitivity to the drug. On the basis of these results, the dosage of triazolam for elderly persons should be reduced on average by 50 percent.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Double-Blind Method; Female; Humans; Male; Memory; Middle Aged; Psychomotor Performance; Triazolam
PubMed: 2034245
DOI: 10.1056/NEJM199106133242403