CLINICAL, ELECTROENCEPHALOGRAPHIC, AND PHARMACOKINETIC STUDIES OF A WATER-SOLUBLE BENZODIAZEPINE, MIDAZOLAM MALEATE

Five subjects lost consciousness with midazolam maleate, 10 mg. The onset of sleep, as measured by cessation of counting or loss of lash reflex, occurred after 30 to 97 sec. The onset of sleep was followed in every subject by a brief period of apnea, with an average duration of 18 sec. The durations of sleep from the commencement of infusion to the time of opening the eyes on command averaged 4 min, 23 sec, with a range of 3 min, 20 sec-5 min, 45 sec. All subjects were oriented with respect to time and place 19 min after commencement of the infusion, and this occurred in one subject as early as 6 min after commencement of the infusion. Systolic and diastolic blood pressures, pulse rate and respiratory rate did not change with drug administration. Even at peak plasma levels, there was no clinically significant alteration in cardiovascular variables. Four of the subjects reported some dizziness for as long as an hour post-medication, while one denied experiencing any dizziness. Each could stand unsupported with his eyes closed two hours after drug infusion. No subject reported unpleasant or frightening experiences during the study. There was no complaint of pain on infusion of the medication. The infusion sites were inspected after 24, 48, and 72 hours, and there was no evidence of phlebitis.