The bioavailability of diazepam (10 mg) was compared in a doubleblind cross–over manner in two studies on 15 healthy subjects. Serum diazepam levels were measured and the occurrence of pain at the injection site as well as fatigue was noted 20, 40, 60, 90 and 180 min. after the administration of 0.15 mg/kg of diazepam to seven subjects. Three intramuscular preparations were used: valium® (Roche), diapam® (Orion) and 301–K 2/74 (Orion). The last–mentioned preparation contained only half the propylene glycol contained in the other preparations, and polyethylene glycol (Macrogol) was the main solvent. The other eight subjects were similarly tested after the administration of diazepam orally, intramuscularly and rectally. In addition the precipitation of diazepam from intravenous solutions was investigated with diazepam in both solvents. Bioavailability and fatigue were similar after each treatment. 301–K 2/74 and its solvent placebo caused significantly less pain in the thigh than valium® or diapam®. The results suggest that an intramuscular injection of diazepam, deep into vastus lateralis muscle, and rectal and oral administration result in comparable bioavailability and clinical effects. A reduction in the amount of propylene glycol solvent used was associated with less pain at the injection site. When diapam® was injected into an infusion tube at a rate of 5 mg/min., the rate of infusion of 5 % glucose or 0.9 % saline had to be as fast as 20 ml/min. in order to prevent visible precipitation, whereas no precipitation was observed when 301–K 2/74 was injected at the 5 mg/min. rate into infusions moving at 5 ml/min. Further clinical studies with intramuscular and intravenous 301–K 2/74 are warranted.

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