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1 The pharmacokinetic and some pharmacodynamic characteristics of a single oral dose of 100 mg trazodone were compared in young and elderly volunteers. 2 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. 3 The terminal phase half-life of trazodone was significantly prolonged (P < 0.05) and area under the plasma concentration-time curve was significantly larger (P < 0.01) in the elderly. Apparent oral clearance was significantly reduced (P < 0.01) in the elderly. 4 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. 5 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.

Summary:The pharmacokinetics of flupirtine after a single oral dose of 100mg have been studied in patients with moderate renal impairment and in healthy elderly subjects aged 66-83 years. Mean elimination half-life of flupirtine was higher in elderly patients than in younger normal subjects, and this was associated with an increased maximum serum concentration and reduced clearance. The mean half-life in patients with renal impairment was higher than in normal subjects.There was no correlation between observed elimination half-life and degree of renal impairment, but the creatinine clearance of most patients fell in a narrow range between 43 and 60 ml/min. In the light of these results and until further information is available, it would be prudent to start treatment of patients who are elderly or have evidence of renal impairment with half the dose of flupirtine recommended for younger patients with normal renal function.

No abstract

Summary:The pharmacokinetics of chlortenoxicam, a new non-steroidal anti-inflammatory drug, have been compared in young and elderly healthy human volunteers. Chlortenoxicam was found to have a relatively short mean elimination half-life of about 4 hours, with considerable inter-subject variability, but there was no significant difference between young and elderly subjects. There was no evidence of accumulation with repeated administration. No unchanged chlortenoxicam was found in urine from any subject, suggesting that it undergoes extensive metabolism in man.

No abstract

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.

Clinical research misdemeanours include a broad spectrum of misdeeds that misappropriate an unfair advantage or harm the rights of others. There is no internationally accepted definition of such malpractices and no generalized procedure to facilitate their reporting or correction. Those who do report research misdemeanours are often stigmatized as ‘whistleblowers’, a term that has acquired many negative connotations. Frequently, whistleblowers encounter many personal conflicts and/or may suffer victimization in their working environment. There remains a need for an internationally harmonized approach to manage these unacceptable problems. Resolution of such important issues should be catalysed by the impending need for European Union states to implement Good Clinical Practice Directive 2001/20/EC into national law.