The Influence of the Route of Administration on the Clinical Action of Diazepam

Abstract

It is generally agreed that absorption of drugs occurs more rapidly following their intramuscular injection than when given by mouth.'-3 This is the basis for the giving of premedicants by injection, which although challenged by Inglis & Barrow in 1965,4 is still widely practised.Recently, in a pilot study, McCaughey & Dundee' found better sedation when 10 mg diazepam was given by mouth than following its intramuscular injection, but their investigation was carried out on a small number of patients. In view of the importance of this finding a large-scale study was undertaken involving both the oral and intramuscular routes, in which neither the patient nor the observer knew whether the capsule or injection was the active drug. As a result of this, and studies of blood diazepam levels, a further smaller investigation was initiated when injections were all given by a doctor.The findings involve many aspects of the action of diazepam and this presentation is designed to show the relative merits and demerits of the two routes of administration. No attempt was made to compare the action of diazepam with that of other premedicants or a placebo. Method PatientsThe patients were fit adult women from one hospital unit, scheduled for morning minor gynaecological operations. They were first questioned as to their use of tranquillisers or sedatives, and if they had been on long-term therapy within the previous month or had been given a hypnotic on the night prior to operation they were excluded from the study. DrugsEach patient was given one capsule by mouth and a 2 ml injection about 90 minutes

Bioavailability and Dose Proportionality of Intramuscular Diazepam Administered by Autoinjector

“…12 The infrequent mild discomfort at the IM injection site was notable, particularly because early reports describe unacceptable pain upon IM injection of diazepam in the thigh. 23,24 Such pain was not observed in the present studies. Of the 92 injections administered in both studies, 9 (10%) injections were associated with generally mild injection site pain.…”

“…The infrequent mild discomfort at the IM injection site was notable, particularly because early reports describe unacceptable pain upon IM injection of diazepam in the thigh 23,24 . Such pain was not observed in the present studies.…”

Polyethylene Glycol as a Solvent for Diazepam: Bioavailability and Clinical Effects after Intramuscular Administration, Comparison of Oral, Intramuscular and Rectal Administration, and Precipitation from Intravenous Solutions

“…However, MCCAUGHEY & DUNDEE (1972) reported that better and more rapid sedative effects are achieved after oral than after intramuscular administration. Since facilities for estimating drugs in plasma or serum have improved it has been demonstrated that definitely higher plasma and serum levels of diazepam are achieved when the drug is administered by mouth than when the same amount of diazepam is injected intramuscularly into the buttock, thigh or shoulder (KANTO 1974;ASSAF et al 1975;KORTTILA & LINNOILA 1975a). Furthermore, pain frequently occurs after an intramuscular injection of diazepam (ASSAF et al 1975;KORTTILA & LINNOILA 1975b).…”

Drug Metabolism in Gastrointestinal Tract

“…The various factors responsible for variability among the population are genetic polymorphism Hruby and Anzenbacher, 1997;Board et al, 1998;Ozawa, 1998;Neber and Roe, 2001;Lamba et al, 2002;Miners et al, 2002;Nagar and Remmel, 2006;Hildebrandt et al, 2007), age (Wilkinson, 1997;Benedetti et al, 2007), gender (Shapiro et al, 1995;Gutmann et al, 2005), species (Hruby and Anzenbacher, 1997), strain (Chen et al, 2005;Wang et al, 2006;Joseph et al, 2007), diet and environmental factors (Wilkinson, 1997;Nowell et al, 1999;Huang and Lesko, 2004;Felton and Malfatti, 2006), induction and inhibition of drug-metabolizing enzymes Lin and Lu, 1998;Lu, 1998;Handschin and Meyer, 2003;Xu et al, 2005), and induction and inhibition of drug influx and efflux transporters (Suzuki and Sugiyama, 2000;Kim, 2002;Lau et al, 2004;Endres et al, 2006;Lin, 2007). Also, physiological conditions such as pregnancy (Larrey et al, 1986;Tsutsumi et al, 2001), pathological conditions or disease states (Wilkinson, 1997), route of administration (Assaf et al, 1975;Shand et al, 1975;Houston and Levy, 1976), dosing strength, and the dosage form can also impact drug-drug interactions. Induction and inhibition of the drug-metabolizing enzymes and efflux transporters by ligand-based NR activation are discus...…”