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At least 19 recordsLinked to original sources
PubMed1997

Plasma concentrations of trazodone and m-chlorophenylpiperazine at steady state can be predicted from those after an initial dose of trazodone.

1. The authors studied the correlations between plasma concentrations of trazodone and mCPP at steady state and those after an initial dose of trazodone. 2. Fifteen depressed patients received trazodone 150 mg at bedtime for 3 weeks, and blood samplings were taken 12 h after the initial dose and 12 h after the last dose at each week. Plasma concentrations of trazodone and mCPP were measured by high-performance liquid chromatography. 3. Plasma concentration of mCPP, but not trazodone, was significantly higher at each week than after initial dosing. 4. For both trazodone and mCPP, significant linear relationships were found between plasma concentration after initial dosing and the average of 3 weeks' plasma concentrations. 5. The present study thus suggests that plasma concentrations of trazodone and mCPP at steady state can be predicted from those after an initial dose of trazodone.

Adult↗
PubMed1990

Antidepressant-like effects of trazodone on a behavioral screen are mediated by trazodone, not the metabolite m-chlorophenylpiperazine.

Trazodone is an atypical antidepressant drug (i.e. blocks neither monoamine uptake nor monoamine oxidase) which tests as an antidepressant drug on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement by increasing the reinforcement rate and decreasing the response rate. m-Chlorophenylpiperazine (m-CPP) is a 5-HT1B and 5-HT1C agonist, weak 5-HT2 antagonist, and trazodone metabolite. It has been suggested that formation of m-CPP is responsible for the antidepressant action of trazodone. Administration of m-CPP (1-10 mg/kg i.p.) 60, 30 or 10 min before the behavioral session did not mimic the reinforcement rate-increasing effects of trazodone (10-20 mg/kg i.p.) on rats performing under the DRL 72-s schedule of water reinforcement. Pretreatment with proadifen (50 mg/kg i.p.), an inhibitor of trazodone metabolism, caused a greater than 30-fold leftward shift in the dose-response curve for both the reinforcement rate and the response rate. These results suggest that the parent compound and not the trazodone metabolite m-CPP, mediates the antidepressant-like effects of trazodone on DRL 72-s behavior.

Animals↗
PubMed1988

Effects of a controlled-release formulation of trazodone on psychomotor and autonomic functions in healthy volunteers: comparison with trazodone (conventional formulation), amitriptyline and placebo.

Eight healthy male volunteers participated in four experimental sessions. In each session the subjects ingested a single dose of one of the following drugs: trazodone (controlled-release formulation), trazodone (conventional formulation), amitriptyline and placebo. Both trazodone and amitriptyline reduced subjectively rated alertness and increased digit cancellation time, and amitriptyline also reduced critical flicker fusion frequency. Both antidepressants reduced salivation, trazodone also caused miosis. There were no consistent differences between the effects of the two formulations of trazodone. The results of the psychological tests are indicative of the sedative properties of the antidepressants. It is likely that the reduction in salivation and pupil diameter by trazodone reflect alpha-adrenoceptor blockade, whereas the reduction in salivation by amitriptyline may be due to both cholinoceptor and alpha-adrenoceptor blockade.

Administration, Oral↗
PubMedDate not supplied

Effect of dosage and route of administration of trazodone on cerebral concentration of 1-m-chlorophenylpiperazine in rats. Kinetics of trazodone biotransformation in rats.

The levels of trazodone (TRZ) and its metabolite, 1-m-chlorophenylpiperazine (CPP) in the rat brain were tested after single and multiple administration of TRZ ip or po. After a single oral dose and after multiple ip or po administration of TRZ, the brain level of CPP exceeded markedly that of the parent compound. Some of pharmacokinetic parameters of TRZ and CPP were significantly changed after chronic treatment. As the biological effect of CPP is opposite to that of its parent compound, the high level of metabolite in the central nervous system may affect strongly the pharmacological activity of TRZ.

Animals↗
PubMed1999

Pharmacokinetics of trazodone and its major metabolite m-chlorophenylpiperazine in plasma and brain of rats.

Sprague-Dawley rats were used as models for single trazodone administration (males), continuous adminstration and dose proportionality experiments (males, females, pregnant females). Plasma and brain tissue were analysed for trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP). Fetal exposure to trazodone and m-CPP was assessed and differences in their steady-state plasma concentration were sought between adult males and females. Both trazodone and m-CPP rapidly appeared in plasma and brain tissue following a single intraperitoneal trazodone dose with brain concentrations exceeding those in plasma. Plasma concentrations of m-CPP were lower than those of trazodone but exceeded them in brain tissue. Chronic administration using osmotic mini-pumps revealed a significant linear relationship between trazodone concentration in plasma and brain at steady-state (r=0.96, p<0.0001). No simple relationship was found between plasma and brain tissue concentration for m-CPP. In contrast to observations following single trazodone administration, m-CPP concentrations at steady-state were lower than trazodone concentrations in brain tissue, suggesting a lack of stationarity in the disposition of trazodone over time. No significant differences in plasma or brain tissue drug concentrations relative to administered trazodone dose were observed between male and female rats, nor between pregnant and non-pregnant females. Trazodone and m-CPP were both detected in fetal and placental tissues, with placenta having the highest concentrations. The data suggest that neuropharmacological studies of trazodone could yield different results depending upon the route and schedule of drug administration. Maternally administered trazodone, like many other antidepressants, is distributed to fetal tissues in rodents, reaffirming the need for caution in treating pregnant women with psychoactive drugs.

Journal Article↗
PubMed1996

Efficacy of treatment with trazodone in combination with pindolol or fluoxetine in major depression.

Fluoxetine, a selective serotonin (5-HT) reuptake inhibitor (SSRI), and trazodone, a heterocyclic antidepressant, are effective in the treatment of major depression and treatment resistant depression (TRD). Chronic treatment with both drugs causes increases in extracellular 5-HT through 5-HT reuptake inhibition and desensitization of inhibitory 5-HT1A autoreceptors. It has been shown that pindolol, a serotonin (5-HT)1A-receptor antagonist, may shorten the latency of onset of SSRIs in depression. The aim of the present study was to examine whether pindolol may increase the efficacy of a subtherapeutical dosage of trazodone in the treatment of major depression and TRD, defined according to the Thase and Rush criteria (1995). Thirty-three major depressed inpatients of whom 26 with TRD participated in this study. Ten days after hospitalization, treatment with trazodone 100 mg/day was started. After 1 week trazodone treatment, patients were randomized-using a double blind placebo controlled design-to receive trazodone 100 mg/day+placebo; trazodone 100 mg/day+pindolol 7.5 mg/day: or trazodone 100 mg/day+fluoxetine 20 mg/day and treated during 4 weeks. The 17-item Hamilton Depression Rating Scale (HDRS) was used as outcome measure. It was found that trazodone+pindolol was as effective as trazodone+fluoxetine in the treatment of major depression and TRD and significantly more effective than trazodone+placebo. Using an outcome measure of 50% reduction in the HDRS, we found that 72.5% of the depressed patients treated with trazodone+pindolol and 75% of depressed patients treated with trazodone+fluoxetine showed a clinically significant response compared with 20.0% of trazodone+placebo-treated patients.

Adult↗
PubMed1994

Trazodone. A review of its pharmacology, therapeutic use in depression and therapeutic potential in other disorders.

Trazodone is a triazolopyridine derivative, chemically and pharmacologically unrelated to other currently available antidepressants. It possesses antidepressant, and also some anxiolytic and hypnotic activity. Results from a small number of short term (4 to 6 weeks) comparative studies in a total of 320 evaluable elderly patients with major depression, suggest that trazodone at therapeutic doses is superior to placebo and as effective as amitriptyline, imipramine, fluoxetine and mianserin in relieving depressive symptoms. Trazodone has also been successfully used in a small number of patients with depression and pre-existing cardiovascular disease. More recently, trazodone has been used as a hypnotic for psychotropic-induced or other insomnias with some success. However, further clinical experience is needed to confirm these preliminary results. In the elderly, maximum tolerated doses of trazodone are 300 to 400 mg/day, although higher doses of up to 600 mg/day are tolerated by younger patients. Drowsiness is commonly reported, but the incidences of both anticholinergic and cardiovascular effects were notably lower in elderly patients treated with trazodone compared with older tricyclic antidepressants. However, undesirable effects such as orthostatic hypotension, arrhythmias and priapism need to be closely monitored. In comparison with other currently available agents, particularly the tricyclic antidepressants, trazodone is relatively safe in overdose. In terms of therapeutic efficacy, trazodone appears to confer little advantage over other available antidepressants. While limited data suggest that trazodone may be better tolerated than older tricyclic antidepressants, especially in the elderly, there is a paucity of data at present comparing trazodone with the secondary amine tricyclic agents, serotonin reuptake inhibitors or moclobemide. Bearing this in mind, trazodone may be of use in elderly patients in whom anxiety and insomnia are problematic, and in those patients who are unresponsive to or cannot tolerate therapy with other agents. Studies are also required to define the place of trazodone in long term prophylactic therapy for recurrent depression. Future trials comparing both its efficacy and tolerability with those of newer agents will ascertain whether trazodone becomes a first line agent within these subsets of elderly patients.

Aged↗
PubMed2005

A review of the evidence for the efficacy and safety of trazodone in insomnia.

OBJECTIVE: Trazodone, a triazolopyridine antidepressant, is currently the second most commonly prescribed agent for the treatment of insomnia due to its sedating qualities. Given trazodone's widespread use, a careful review of the literature was conducted to assess its efficacy and side effects when given for treatment of insomnia. DATA SOURCES: In April 2003, a MEDLINE search was conducted using the search terms trazodone and insomnia and trazodone and sleep and restricted to 1980-2003, human subjects, and English language. As trazodone has been implicated in cardiac disorders, a further search was conducted using the term cardiac and trazodone. STUDY SELECTION: All clinical trials that measured any endpoint for insomnia efficacy were included in the assessment. A total of 18 studies were identified from the literature search. In addition, commonly used texts were consulted for information regarding adverse effects related to trazodone. DATA EXTRACTION: Because so few studies were identified by the literature search, all were evaluated and described. DATA SYNTHESIS: Evidence for the efficacy of trazodone in treating insomnia is very limited; most studies are small, conducted in populations of depressed patients, raise issues of design, and often lack objective efficacy measures. Side effects associated with trazodone are not inconsequential, with a high incidence of discontinuation due to side effects, such as sedation, dizziness, and psychomotor impairment, which raise particular concern regarding its use in the elderly. There is also some evidence of tolerance related to use of trazodone. CONCLUSION: Given the relative absence of efficacy data in patients with insomnia and the adverse events associated with trazodone's use in general, it is uncertain whether the risk/benefit ratio warrants trazodone's use in nondepressed patients with insomnia.

Adult↗
PubMedDate not supplied

Antidepressant properties of trazodone.

The chemistry, pharmacokinetics, biochemistry and pharmacology, clinical trials, adverse effects, FDA-approved indications, and availability and cost of trazodone hydrochloride, a triazolopyridine antidepressant, are reviewed. Trazodone is nearly completely absorbed after oral administration; although food delays absorption and reduces peak serum concentration, total area under the plasma concentration-time curve is not altered. Trazodone has biphasic elimination, with a redistribution half-life of about one hour and an elimination half-life of 10-12 hours. Trazodone is nearly completely metabolized hepatically by hydroxylation and oxidation to metabolites that are probably inactive. Trazodone is less potent but more selective than conventional tricyclic antidepressants; at low doses, trazodone acts as a serotonin antagonist, while at high doses it acts as a serotonin agonist. Trazodone has been compared with imipramine, amitriptyline, desipramine, and placebo in controlled clinical trials and found to be an effective antidepressant. Trazodone causes significantly fewer anticholinergic side effects than does imipramine. Trazodone has few cardiovascular side effects. In patients ingesting toxic amounts of trazodone, no deaths have been reported unless other drugs were present or ingested concomitantly. The usual adult daily dose of trazodone hydrochloride is 150-400 mg given in two divided doses. Trazodone is an effective antidepressant with a low incidence of serious adverse effects. It may be particularly useful in certain depressed patients who are intolerant of anticholinergic effects of other antidepressants, have cardiac conduction disturbances, or who do not respond to treatment with tricyclic antidepressants and in whom electroshock therapy is contraindicted.

Animals↗
PubMed2003

Trazodone for erectile dysfunction: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of trazodone in the treatment of erectile dysfunction (ED) in a meta-analysis. METHODS: The data sources used were Medline and the Cochrane Library databases (January 1966 to May 2002), bibliographies of retrieved articles and review articles, and conference proceedings and abstracts. Trials were eligible for inclusion in the review if they included men with ED, compared trazodone with a control, were randomized, of > or = 7 days' duration and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. RESULTS: Six trials (comprising 396 men) met the inclusion criteria; they consisted of heterogeneous populations, were small, brief and in some cases methodologically weak. Three of the six trials showed an apparently clinically meaningful benefit of trazodone for ED compared with placebo, the differences being statistically significant in two. In pooled results, trazodone monotherapy appeared more likely than placebo to lead to a 'positive treatment response', although this difference was not statistically significant (37% vs 20%; relative benefit increase, 1.6; 95% confidence interval, CI, 0.8-3.3). Subgroup analyses suggested that men with psychogenic ED might be more likely to benefit from trazodone than those with mixed or physiological ED. The efficacy of trazodone also appeared greater at higher doses (150-200 vs 50 mg/day). Men randomized to trazodone were not significantly more likely than those receiving placebo to withdraw for any reason or for an adverse event, or to have specific adverse events, but wide CIs could not exclude a greater risk of these adverse outcomes with trazodone. Specific adverse events with trazodone included dry mouth (19%), sedation (16%), dizziness (16%) and fatigue (15%). CONCLUSION: Trazodone may be helpful in men with ED, possibly more so at higher doses, and in men with psychogenic ED. Future high-quality trials should compare trazodone with placebo and other therapies in men with depression and psychogenic ED.

Adult↗
PubMed2004

Therapeutic drug monitoring of trazodone: are there pharmacokinetic interactions involving citalopram and fluoxetine?

OBJECTIVE: Therapeutic drug monitoring (TDM) of the new generation antidepressants is subject of controversial discussion. Nonetheless, TDM may safeguard against drug-drug interactions, can be used to control compliance and is valuable in the investigation of overdose. METHOD: The aim of this prospective study was to investigate serum levels of trazodone when prescribed as monotherapy or when used in combination with the selective serotonin reuptake inhibitors citalopram and fluoxetine in a simultaneous assay using high-performance liquid chromatography (HPLC). Over a 1-year period, we studied 97 patients (63 females) with depressive syndrome who were subdivided into 3 main diagnostic groups. Fifty-two patients were smokers, the mean age was 39.9 years and the mean weight was 72.4 kg; 40 patients were taking trazodone alone, 41 trazodone in combination with citalopram and 16 patients trazodone in combination with fluoxetine. RESULTS: The use of citalopram and fluoxetine in combination with trazodone had no significant impact on trazodone serum levels, and the same was true for differences in body weight and smoking behavior. On the other hand, age and sex had a significant influence on the pharmacokinetic pattern of trazodone, causing higher concentrations in females and in older patients. Since the polypharmacy investigated did not change the serum levels of trazodone, we assume that there is no metabolic interaction between trazodone and citalopram and trazodone and fluoxetine. We observed none of the adverse effects which might have been expected, including dizziness, severe headache, daytime sedation, fatigue or the serotonin syndrome even in a mild form. CONCLUSION: A "double-tracked" antidepressive treatment using trazodone and the SSRIs citalopram and fluoxetine is associated with a wide safety margin.

Adult↗
PubMed2004

Trazodone for agitation in dementia.

BACKGROUND: Behavioural and psychiatric disturbances affect at least 50% of people with Alzheimer's disease and other dementias. Neuroleptic drugs are extensively prescribed to treat behavioural manifestations of dementia in spite of only modest efficacy and a high frequency of adverse effects. There is clearly a need for safer and more effective remedies. Trazodone is a psychoactive compound with sedative and antidepressant properties, and with mixed serotonin agonist and antagonist effects. Functional serotonergic deficits may be related to the genesis of behavioural disturbances in dementia. OBJECTIVES: To determine the clinical efficacy and safety of trazodone, for any type of behavioural or psychological cognition in people with dementia without an additional diagnosis of depression. SEARCH STRATEGY: Trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 1 June 2004 using the terms trazodon*, beneficat, desirel, sideril, trazodil, trazalon. This register contains records from all major health care databases and many ongoing trials databases, and is updated regularly. SELECTION CRITERIA: All unconfounded, double-blind, randomised controlled trials, comparing trazodone with placebo in managing behavioural and psychiatric symptoms (except depression) in any type of dementia. DATA COLLECTION AND ANALYSIS: Available data for this analysis were extracted from the two included studies and odds ratios or average differences, with 95% confidence intervals, calculated. Intention-to-treat analysis was undertaken where possible. MAIN RESULTS: Two studies were included, comprising 104 participants with dementia. The trials differed in design - one being a parallel-group study of patients with Alzheimer's disease (Teri 2000) and one being a cross-over study of patients with frontotemporal dementia (Lebert 2004). It was not possible to pool the data. The studies were respectively of 16 and 6 weeks duration, using trazodone from 50 to 300mg daily. Both trials examined global clinical state, behavioural disturbances and cognitive function. Teri 2000 also assessed activities of daily living and caregiver burden. Compared with placebo, the use of trazodone was not associated with statistically significant benefits for behavioural manifestations as measured by various rating scales (ABID, CERAD-BRSD,CMAI, NPI). Analysis of changes from baseline for clinical impression of change and for cognitive function did not produce statistically significant results in favour of trazodone. A variety of adverse effects were recorded with no significant differences between trazodone and placebo. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend the use of trazodone as a treatment for behavioural and psychological manifestations of dementia. In order to assess effectiveness and safety of trazodone, longer-term trials are needed, involving larger samples of participants with a wider variety of types and severities of dementia.

Antidepressive Agents, Second-Generation↗
PubMed2004

Effects of the antidepressant trazodone, a 5-HT 2A/2C receptor antagonist, on dopamine-dependent behaviors in rats.

RATIONALE: 5-Hydroxytryptamine, via stimulation of 5-HT 2C receptors, exerts a tonic inhibitory influence on dopaminergic neurotransmission, whereas activation of 5-HT 2A receptors enhances stimulated DAergic neurotransmission. The antidepressant trazodone is a 5-HT 2A/2C receptor antagonist. OBJECTIVES: To evaluate the effect of trazodone treatment on behaviors dependent on the functional status of the nigrostriatal DAergic system. METHODS: The effect of pretreatment with trazodone on dexamphetamine- and apomorphine-induced oral stereotypies, on catalepsy induced by haloperidol and apomorphine (0.05 mg/kg, i.p.), on ergometrine-induced wet dog shake (WDS) behavior and fluoxetine-induced penile erections was studied in rats. We also investigated whether trazodone induces catalepsy in rats. RESULTS: Trazodone at 2.5-20 mg/kg i.p. did not induce catalepsy, and did not antagonize apomorphine (1.5 and 3 mg/kg) stereotypy and apomorphine (0.05 mg/kg)-induced catalepsy. However, pretreatment with 5, 10 and 20 mg/kg i.p. trazodone enhanced dexamphetamine stereotypy, and antagonized haloperidol catalepsy, ergometrine-induced WDS behavior and fluoxetine-induced penile erections. Trazodone at 30, 40 and 50 mg/kg i.p. induced catalepsy and antagonized apomorphine and dexamphetamine stereotypies. CONCLUSIONS: Our results indicate that trazodone at 2.5-20 mg/kg does not block pre- and postsynaptic striatal D2 DA receptors, while at 30, 40 and 50 mg/kg it blocks postsynaptic striatal D2 DA receptors. Furthermore, at 5, 10 and 20 mg/kg, trazodone blocks 5-HT 2A and 5-HT 2C receptors. We suggest that trazodone (5, 10 and 20 mg/kg), by blocking the 5-HT 2C receptors, releases the nigrostriatal DAergic neurons from tonic inhibition caused by 5-HT, and thereby potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.

Animals↗
PubMed1991

Pathophysiology of prolonged penile erection associated with trazodone use.

Treatment with the antidepressant trazodone has been associated with the occurrence of prolonged penile erection and priapism. To evaluate the effect of trazodone on erection we monitored the periodic physiological sleep-related erections in 6 healthy volunteers in a double-blind crossover study comparing the effect of trazodone, trimipramine (a tricyclic antidepressant) and placebo. In addition, to determine the effects of trazodone on the neurovascular control of penile smooth muscle we performed in vitro studies on corpus cavernosum tissue obtained from patients undergoing penile prosthesis implantation. Trazodone significantly increased the total interval of nocturnal erectile activity, while trimipramine had no effect. During the high dose treatment (nights 4 and 5) the average duration of erectile activity per night with placebo was 158 +/- 41 minutes (mean +/- standard deviation) for night 4 and 177 +/- 21 minutes for night 5. During trazodone treatment the erectile activity per night was significantly prolonged to 285 +/- 115 minutes during night 4 and 232 +/- 86 during night 5 (p less than 0.01). Analysis of the erectile activity in relation to the rapid eye movement sleep period during which erectile activity usually occurs revealed that the detumescence phase of erection, under sympathetic control, was significantly prolonged an average of 2.4 times by trazodone compared to placebo (p less than 0.05). In vitro, trazodone at concentrations comparable to those reached in plasma significantly impaired corporeal smooth muscle contractions elicited by electrical stimulation of adrenergic nerves and antagonized contractions induced by exogenous norepinephrine. We conclude that trazodone can enhance penile erection in man and propose a mechanism related to the alpha-adrenoceptor blocking properties of trazodone by interference with the sympathetic control of penile detumescence.

Adolescent↗
PubMed2000

The antinociceptive effect of trazodone in mice is mediated through both mu-opioid and serotonergic mechanisms.

The antinociceptive effects of trazodone (a triazolopyridine derivative with antidepressant activity) and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. Mice were tested with a hotplate analgesia meter. Trazodone induced a dose-dependent antinociceptive effect following i.p. administration. The ED(50) for mice in the hotplate assay for trazodone was 24.8 mg/kg (9.8; 67.4; 95% CL). The effect of opioid, adrenergic and serotonergic receptor antagonists was examined as to their ability to block trazodone antinociception. Trazodone-induced antinociception was significantly inhibited by naloxone, beta-FNA and naloxonazine, but not by nor-BNI or naltrindole, implying involvement of mu1- and mu2-opioid mechanisms. When adrenergic and serotonergic antagonists were used, metergoline (p<0.05) but not phentolamine or yohimbine, decreased antinociception elicited by trazodone, implying a clear 5-HT mechanism of antinociception. When trazodone was administered together with various agonists of the opioid receptor subtypes, it significantly potentiated antinociception mediated by mu1- and mu2- opioid receptor subtypes. Summing up these results, we conclude that the antinociceptive effect of trazodone is mainly influenced by the mu1- +mu2-opioid receptor subtype combined with the serotonergic receptor. These results explain the diffuse clinical use of trazodone in the management of some pain syndromes, and in opioid- and alcohol-detoxification programs, but raise questions regarding a possible 'indirect' opioid-dependence induced by trazodone itself.

Analgesics↗
PubMed1992

Single dose pharmacokinetics of trazodone in healthy subjects.

Eight healthy subjects were administered trazodone-HCl orally (100 mg) with and without food and by infusion in a three way cross-over study. Unchanged trazodone was determined in serum and urine by high performance liquid chromatography after an alkaline extraction. Absorption of trazodone was irregular in fasting subjects and improved after food intake. Food intake significantly decreased the maximum serum concentrations of trazodone from 1.88 +/- 0.42 to 1.47 +/- 0.16 micrograms/ml, and increased the time for reaching maximum concentration from 1.3 +/- 0.8 hr to 2.0 +/- 1.5 hr. No differences were observed in the total amount of trazodone absorbed with or without food with bioavailability values of 65 +/- 6 and 63 +/- 4 per cent, respectively. The apparent volume of distribution and total body clearance for trazodone were estimated to 0.84 +/- 0.16 l/kg and 5.3 +/- 0.9 l/hr, respectively. The terminal elimination half-life of 7.3 +/- 0.8 hr showed no significant differences between the different ways of administration. Urinary excretion of unchanged trazodone during 26 hr was less than 0.13 per cent of the administered dose, suggesting a high degree of trazodone metabolism. Earlier statements of enterohepatic circulation of trazodone and pharmacokinetic differences between males and females were not confirmed by the present study. Due to the irregular absorption in fasting subjects, trazodone should preferably be administered after food.

Absorption↗