Plasma amitriptyline level after acute administration, and driving performance in healthy volunteers



Aims:  Amitriptyline triggers the impairment of cognitive and motor functions and has been confirmed to have harmful effects on driving performance. Although interindividual differences in plasma concentration may cause variations in driving performance, the relationship between plasma amitriptyline concentration and its effect on driving performance has not been completely elucidated. Thus, the aim of the present study was to assess the influence of individual pharmacokinetic differences on driving performance and cognitive functions.

Methods:  In this double-blinded study, 17 healthy male volunteers were given an acute, single, 25-mg dose of amitriptyline. The subjects were assigned three driving simulator tasks, three cognitive tasks, and the questionnaire of the Stanford Sleepiness Scale at the baseline and at 4 h after dosing. The plasma amitriptyline concentrations were measured on high-performance liquid chromatography.

Results:  A significant positive correlation was observed between the plasma amitriptyline concentration and road-tracking performance (r = 0.543, P < 0.05). There was no significant correlation between the plasma amitriptyline concentration and other driving performance, cognitive functions, and subjective somnolence.

Conclusions:  Amitriptyline produces a concentration-related impairment on road-tracking performance. Therapeutic monitoring of amitriptyline would be useful for predicting the difficulties involved while driving.