Comparative bioavailability of trazodone formulations using stable isotope methodology.
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The bioavailability of trazodone, a new antidepressant, from 50 mg dividose (A) or film-sealed (B) tablets relative to an oral solution was determined in six healthy male subjects using 50 mg of D4-trazodone as a stable isotope labelled standard. Concentrations of trazodone and D4-trazodone were measured by GCMS. The pharmacokinetics of trazodone and D4-trazodone were identical indicating no isotope effect. For formulation A, B and solution, the relative (trazodone/D4-trazodone) Cmax values were 0.84 +/- 0.09, 0.90 +/- 0.05 and 1.05 +/- 0.04. The relative bioequivalence of the dosage formed with a power of 85% (power by conventional ANOVA was 54%). Among subjects % relative standard deviations (RSD) for the D4-trazodone AUC values, a measure of intra-subject variability, were 6 to 38% while the % RSDs by period, a measure of inter-subject variability, were 26 to 55%. (+info)
An evaluation of possible interactions between ethanol and trazodone or amitriptyline.
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The pharmacodynamic effects of single doses of trazodone (100 mg), amitriptyline (50 mg) or placebo either alone or with ethanol (0.5 ml/kg) were investigated in six healthy volunteers in a double-blind crossover study. Plasma concentrations of the drugs and ethanol were also measured. Pharmacodynamic tests were critical flicker fusion frequency threshold (CFF), choice reaction time (CRT), manual dexterity, a digit span test and visual analogue scales. Blood ethanol concentrations were not influenced by the co-administration of either antidepressant. tmax for trazodone was prolonged by ethanol but the other pharmacokinetic parameters for trazodone and amitriptyline were not influenced by ethanol. Trazodone and amitriptyline caused the expected profound depressant effects on CFF, CRT, manual dexterity and on the rating scales for drowsiness, 'clear-headedness', aggression and disinhibition. Ethanol alone impaired manual dexterity, increased drowsiness, reduced 'clear headedness' and also tended to reduce feelings of aggression. In combination with either trazodone or amitriptyline, ethanol caused little additional effect except in the case of manual dexterity which was further impaired. This result may reflect the profound effects of the antidepressants alone and does not suggest that it is safe for patients receiving antidepressant medication to take ethanolic drinks. (+info)
Heterogeneity of 5-hydroxytryptamine receptors in the rat uterus and stomach strip.
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Experiments were performed using the rat isolated uterus and the rat stomach strip to investigate the effects of 5-hydroxytryptamine (5-HT) on 5-HT receptors in the presence of different antagonists. Amitriptyline, methysergide and trazodone were used to antagonize the response to 5-HT in these tissues. The pA2 value for amitriptyline with 5-HT as the agonist was estimated from the Schild plot analysis and found to differ significantly (P less than 0.05) in the stomach strip (6.36) from that in the isolated uterus (9.06). A similar difference was found using trazodone; here the pA2 value was 6.74 in the stomach strip and 8.49 in the isolated uterus. These results indicate a difference between the two tissues. This difference is discussed in terms of heterogeneity of 5-HT receptors. (+info)
Trazodone enhances sleep in subjective quality but not in objective duration.
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Nine volunteer poor sleepers, of mean age 61 years, took trazodone 150 mg nightly for 3 weeks, preceded by 2 weeks and followed by 1 week of matching blanks, in order to examine the effects of electrophysiologically-recorded and subjectively-rated sleep. The second of the initial weeks of matching blanks served as a baseline week. In the subjective ratings, sleep improved in quality on trazodone, significantly so in the first and second weeks of intake, though with significant rebound insomnia on the second withdrawal night. Trazodone halved the frequency of arousals interrupting sleep, and it reduced the time spent in stage 1 (drowsiness). It increased the duration of slow-wave sleep (stages 3 + 4), with a negative rebound following withdrawal. It reduced the time spent in REM sleep, with a rebound above baseline levels after withdrawal. Trazodone did not change total sleep duration, nor the time required to fall asleep. The effects of trazodone were sustained or became enhanced during the period of intake. They persisted for over 24 h after the last dose, and rebound effects were maximal on the second withdrawal night. (+info)
Pharmacokinetic and pharmacodynamic characteristics of trazodone in the elderly.
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The pharmacokinetic and some pharmacodynamic characteristics of a single oral dose of 100 mg trazodone were compared in young and elderly volunteers. The maximum plasma concentration of trazodone was similar in both age groups. The time to maximum concentration was apparently prolonged in four subjects who swallowed the capsule with a minimal volume of fluid. This may have been due to the capsule being retained in the oesophagus. The terminal phase half-life of trazodone was significantly prolonged (P less than 0.05) and area under the plasma concentration-time curve was significantly larger (P less than 0.01) in the elderly. Apparent oral clearance was significantly reduced (P less than 0.01) in the elderly. Measurement of critical flicker fusion threshold and subjective assessment of alertness using a visual analogue scale, confirmed the sedative effect of trazodone in both age groups. The elderly subjects were less alert for a longer period following drug administration than the young. The differing pharmacokinetic and pharmacodynamic characteristics of trazodone in the young and elderly may be due to an age-related reduction in hepatic drug-metabolising activity, a difference in regional distribution or a change in CNS sensitivity to the drug. (+info)
Liquid-chromatographic determination of two antidepressants, trazodone and mianserin, in plasma.
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Plasma containing trazodone or mianserin was extracted. The organic phase containing trazodone was evaporated and the residue was reconstituted in dilute acid. Mianserin was back-extracted from the organic phase with dilute acid. Both drugs were chromatographed on mu Bondapak C18 columns, with phosphate/acetonitrile as the mobile phase. Peak-height ratios of drug/internal standard were linearly correlated with concentrations between 25 and 2000 micrograms/L for trazodone, and between 25 and 200 micrograms/L for mianserin, with respective between-run CVs of 4.7% and 7.6%. Detection limits were 5 ng. Of some common drugs and metabolites examined, nortriptyline co-elutes with the internal standard used in the trazodone assay, while flurazepam co-elutes with mianserin. Concentrations of trazodone in 26 patients ranged from 73 to 1678 micrograms/L. For two geriatric patients, concentrations were about 2000 micrograms/L. For two overdose patients, they were about 5000 micrograms/L. The concentration of mianserin was 27 micrograms/L for a volunteer treated with a single 40-mg oral dose. (+info)
Trazodone--a new assay procedure and some pharmacokinetic parameters.
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1 A simple and specific procedure is described for the determination of the new anti-depressant trazodone in human plasma utilising reverse-phase HPLC which is sensitive to 20 ng ml-1. 2 Following oral administration of single 50 mg doses of two formulations of trazodone on separate occasions to healthy fasted volunteers, the peak plasma concentration, time to peak concentration, area under the curve, elimination rate constant and half-life were determined. 3 The two formulations are closely similar and they are considered to have comparable bioavailability. (+info)
The interaction of trazodone with rat brain muscarinic cholinoceptors.
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The muscarinic receptor binding of trazodone, a new nontricyclic antidepressant, was compared with established tricyclic antidepressants. The ability to inhibit the binding of [3H]-quinuclidinyl benzilate in vitro was used for comparing atropine-like effects. Trazodone was found to have essentially no activity at the muscarinic acetylcholine binding site in comparison to the tricyclic antidepressants. (+info)