Midazolam, a new water-soluble benzodiazepine, was administered as: i) 5 mg intravenously, ii) a 10-mg oral solution and iii) a 10-mg oral tablet, to six volunteers whose informed consent had been obtained. Midazolam plasma concentrations were measured using an electron-capture gas-liquid chromatographic assay. After 5-mg intravenous midazolam, subjects fell asleep within 1-2 min and continued to sleep for an average of 1.33 h. After oral midazolam intake (solution or tablets), drowsiness appeared after a average of 0.38 h (range 0.25-0.55 h) and sleep continued for an average of 1.17 h. The time to reach peak plasma midazolam concentration after the 10-mg solution dose (0.37 +/- 0.45 h) did not differ significantly ('t' = 2.04, df = 10, p greater than 0.05) from the time to reach peak plasma midazolam level after the 10-mg tablet dose (0.74 +/- 0.45 h). The terminal half-life, (t 1/2), of midazolam in plasma was 1.77 +/- 0.83 h and there was no significant difference between the mean terminal half-life values obtained for the three midazolam formulations. The mean total clearance (Cl), of midazolam after 5-mg intravenous administration was 0.383 +/- 0.0941 . kg-1 . h-1. The first pass effect, F, determined experimentally (0.36 +/- 0.09) indicated the substantial first pass metabolism of midazolam. The percentage of the midazolam dose excreted unchanged in urine in four subjects during the 0-8-h urine collection interval was very small (0.011%-0.028%).

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Summary The alimentary symptoms found in 107 consecutive cases of Parkinsonism have been compared with those found in 96 control subjects. Chewing difficulty, drooling of saliva, dysphagia, frequent heartburn and constipation all occurred significantly more often in Parkinsonism than in controls, and of these symptoms only the incidences of dysphagia and heartburn did not correlate with increasing disability from Parkinsonism. There was relatively little correlation between alimentary symptoms and ætiological type of Parkinsonism, though chewing difficulty occurred particularly in Parkinsonism following encephalitis lethargica, and constipation in paralysis agitans. The alimentary symptoms of Parkinsonism may be due to dorsal vagal nuclear and basal ganglia lesions, and to side effects of drug therapy.

Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose-related anatomical teratogenesis, as valproate is already known to be.