Diazepam and lorazepam differ in potency and in the time-course of their action. As a sedative, diazepam 10 mg is equivalent to lorazepam 2-2.5 mg. Diazepam is better absorbed after oral than after i.m. administrations but this does not apply to lorazepam. The clinical effect and amnesia begin more rapidly with diazepam, but last longer following lorazepam. Lorazepam is more effective than diazepam in blocking the emergence sequelae from ketamine. Lorazepam i.v. is followed by a lesser frequency of venous thrombosis.

Lorazepam has been studied as preanaesthetic medication given by mouth, i.m. and i.v. Sediation and side-effects and the incidence of anterograde amnesia in patients having a standard operation under methohexitone-nitrous oxide-oxygen anaesthesia were assessed. In a preliminary study of three i.m. (2-, 4- and 8-mg) and six oral (1-,2-,2.5-,4-,5- and 8-mg) doses, the optimum dose was found to be 4 mg for patients with an average weight of 60 kg. This dose was studied in detail when given by all three routes and compared with the commercially available 2.5- and 5-mg tablets. Even when given i.v., there was a delay of 30-40 min in the onset of maximum sedative effect and drowsiness persisted for at least 4 h. Although the onset of action by i.m. injection was slightly faster than when the drug was given by mouth this advantage was more than offset by the high frequencies of pain at the site of injection and restlessness which persisted for 20-40 min. Oral lorazepam in doses of 2.5-5.0 mg was a reliable, effective sedative which could be recommended for routine preanaesthetic medication, provided rapid recovery was not essential. Its soporific effect was accompanied by an appreciable incidence of anterograde amnesia.

No abstract

Lorazepam, a new long-acting benzodiazepine, has been in clinical use for about one year. As part of its evaluation as a premedicant it was necessary to correlate plasma levels with clinical assessment after various modes of administration. A method of extracting lorazepam from plasma was obtained from the manufacturers but proved to be unsuitable when large numbers of samples had to be analysed. It involved a number of stages. A similar method was reported by Knowles, Comer and Ruelius. 'In 1975 Gamble and his colleagues2 described a benzene extraction of diazepam from plasma and from this a method of extraction and estimation of lorazepam was evolved. The method involves a single stage benzene extraction with flunitrazepam as the internal standard which allows 40 samples to be extracted in approximately 2+ hours and chromatographed in 5 hours. The method is described in this paper with critiques on its reliability.The blood samples analysed were obtained during the clinical studies reported by Dundee and c011eagues~~~ and Lilburn, Dundee and Moore5 including the long term use of lorazepam.Extraction. 0.5 ml plasma was extracted with 5 ml of 'Ultrar' grade benzene to which 0.5 ml potassium chloride (Analar) and 50 pl of a 150 ng/ml solution of flunitrazepam in benzene had been added. The mixture was shaken for 15 min on a rotary mixer at 45 revlmin and then centrifuged at 4 000 revlmin for 5 min. Four ml of the benzene layer were removed and evaporated to dryness, reconstituted with 50 pl of benzene and 10 , d injected on to the column.A Perkin Elmer F 33 gas chromatograph fitted with a 63Ni electron capture detector (ECD) was used. The column was of borosilicate glass 120 cm in length with an internal diameter of 0.5 cm and packed with 3% OV17 on gas chrom Q 80-100 mesh.Injection temperature 300°C ECD setting 4 Detector temperature 300°C Attenuation 32 Oven temperature 240°C Range 1The carrier gas was oxygen free nitrogen (OFN) at a pressure of 350 kN/mZ. Under these conditions the retention time of lorazepam was 1.9 min and 3.6 min for the internal standardflunitrazepam (Fig. 1). Estimation. A calibration curve is prepared from lorazepam concentrations of 0,25, 50,75, 100 and 125 ng/ml in plasma. The ratio of the lorazepam peak (H) to the internal standard peak (HS) is calculated and the mean of each set of duplicate samples plotted against the lorazepam concentrations. Figure 2 is a typical calibration curve.All observations were carried out in duplicate. From a random batch of 197 plasma lorazepam estimations the duplicate individual levels were Conditions of analysis are:

The pharmacokinetics of methohexital were investigated in ten young adult volunteers and in seven young and seven elderly patients. The latter two groups underwent enflurane and nitrous oxide anesthesia and surgery. Each subject received a bolus dose of 2 mg/kg of methohexital intravenously. Plasma levels of the drug were measured for 8 h after injection by gas chromatography using a nitrogen detector. Anesthesia (combined with surgery) and increase in age did not separately affect the kinetics of the drug; however, the elimination half-life was longer in the elderly patients group than in the young non-anesthetized volunteers.