Plasma diazepam levels after single dose oral and intramuscular administration

Abstract

In a previous study' a surprising finding was that patients premedicated with diazepam (Valium) 10 mg orally were better sedated during the first 90 minutes following administration than when the same dose was given by intramuscular injection into the buttock. This was confirmed in a 'double-blind, double-dummy' study involving 200 comparable patients in whom the drugs were given by the nursing staff.' Plasma diazepam levels were estimated to seek an explanation for these clinical findings, the study being carried out to show the influence of the route of administration on the plasma diazepam levels following a single 10 mg dose. Method Plasma diazepam estimationsThese were done by gas-liquid chromatography following benzene e~traction.~ The method of estimation, its reliability and reproducibility has been described in detail in another paper from this d e~a r t m e n t .~ SubjectsThese were fit young women scheduled for morning minor gynaecological operations who had fasted overnight. Patients who had had diazepam in the previous 4 weeks were excluded as were any patients who, despite the screening, were found to have diazepam or its metabolite in the control plasma sample. Table 1 shows the number of patients. The four groups studied were broadly comparable with respect to average age and weight. The preliminary results following the injection of diazepam into the buttocks by nurses, who normally used a 23 swg (3 cm) needle, led us to repeat part of the investigation when the drug was given into the upper outer quadrant of the buttock by one of the authors using a large 21 swg (4 cm)

Bioavailability and Dose Proportionality of Intramuscular Diazepam Administered by Autoinjector

“…These earlier reports appear to be based on pharmacokinetic studies of IM diazepam injected in the buttocks, or the injection site was not stated. [3][4][5][6][7] Poor diazepam absorption after IM injection in the buttocks is probably due to the fatty tissue and poorer blood flow in the gluteus than in the deltoid and vastus lateralis mucsles. 8 Intramuscular injection of diazepam in the thigh has been reported to result in more rapid systemic absorption than obtained with oral diazepam.…”

Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients.

“…However intravenous administration is practical only if a physician is available. Absorption of diazepam after intramuscular administration is slow, irregular and dependent on the technique of administration and is therefore unsatisfactory in situations where a rapid effect is required (Hillestad et al, 1974;Gamble et al, 1975).…”

Diazepam absorption: Effect of antacids and food

“…Yenous blood samples were drawn into heparinized tubes from an indwelling Butterfly cannula, or by separate venipuncture, prior to diazepam ingestion and at the following times after dosage: 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3,4,6,8,12,24,36, and 48 hr. Plasma was separated and frozen until the time of assay.…”