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The main purpose of this study was to compare the sensitivity of a driving simulator test model (TS2) with a standard on-the-road driving test, after one night treatment with lormetazepam 1 mg, oxazepam 50 mg (as a verum) and placebo. The secondary purpose was to measure the effects of the intended drugs and placebo in the same subject sample, after two treatment nights in the morning and in the afternoon, on on-the-road driving performance. Eighteen healthy male volunteers received the three treatments (2 consecutive nights each) according to a double-blind, three-way crossover design. Time of administration was set at 22.00 hours each night. An on-the-road driving test and a simulator driving test were conducted in the morning following the first night. After the second treatment night, on-the-road driving tests were performed in the morning and in the afternoon. The on-the-road driving test consisted of operating an instrumental automobile over a 100 km highway circuit at a constant speed (90 kmh) and constant steady lateral position between the right lane boundaries. Primary performance measure was the SD of lateral position (SDLP). The simulator test consisted of repeatedly performing 'curve-following' manoeuvres, which was the main tracking control task, while simultaneously reacting to secondary visual signs. Test parameters were the number of correctly executed manoeuvres (TC) and reaction time (RT). Oxazepam 50 mg seriously impaired, and lormetazepam 1 mg slightly impaired, on-the-road driving performance in the morning, both after the first and second treatment night. The drugs produced no significant effects in the afternoon test following the second night. In contrast with these results, neither oxazepam 50 mg nor lormetazepam 1 mg affected simulator tracking control after one night. No deterioration was found for reaction time. Correlational and multiple regression analyses were applied to determine relationships between SDLP, TC and RT. The major conclusion of this study was that the TS2 driving simulator test does not predict residual drug effects in the on-the-road driving test, and seems to be a less sensitive measure of sedative drug-induced impairment in contrast to the on-the-road driving test.KEY wows-Hypnotics, simulated driving, on-the-road driving. INTRODlJCTIONStudies of hypnotics have generally focused on their effects on sleep; however, it is also clear that they have effects which can extend beyond the usual sleep period. Among the risks associated with the use of hypnotics, the most prominent effect is decreased performance during the day following nocturnal administration (Hindmarch, 1980;Volkerts and O'Hanlon, 1986). This hangover or residual effect is not a side-effect, but merely an extension of the drug's primary action. It occurs because hypnotics produce sleepiness, reduce alertness, and thereby reduce performance efficiency. This poses * Author to whom correspondence should be addressed. a crucial problem for hypnotic users who must operate a motor vehicle or other dangerous m...

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ABSTRACI Three further patients are presented who developed evidence of a parenchymal pulmonary disturbance in the course of treatment with amiodarone. In one case the progress of the condition was rapid and ended fatally. Histological examination of the lungs showed evidence of diffuse alveolar damage. The concentration of amiodarone was from four to seven times higher in the lungs than in other organs studied. The concentration of the metabolite desethylamiodarone in the lungs was even higher in relation to other organs studied. The