Absorption of diazepam

Papich, M.G. Alcorn, J. (1995) Absorption of diazepam after its rectal administration in dogs. American Journal of Veterinary Research, 56,1629-1636. 

Several studies have reported that alcohol increases plasma levels of diazepam and that alcohol accelerates the absorption of diazepam, but others have suggested that alcohol has no significant effect on diazepam pharmacokinetics. Plasma levels of brotizolam and clobazam may be increased by alcohol. One study reported that the plasma levels of triazolam were increased by alcohol, but other studies have found only a minimal pharmacokinetic interaction. However, an in vitro study demonstrated that alcohol inhibited the metabolism of triazolam by the cytochrome P450 isoenzyme CYP3A. Another in vitro study reported that the formation of flunitrazepam metabolites was weakly inhibited by alcohol, but a pharmacokinetic study suggested that there was no interaction. Alcohol appears to have minimal effects on the pharmacokinetics of alprazolam, and zopiclone. ... 

Gamble JAS, Gaston JH, Nair SG, Dundee JW. Some pharmacological factors influencing die absorption of diazepam following oral administration. BrJ Anaesth (1976) 48,1181-5. 

Ranitidine, famotidine and nizatidine appear not to inhibit liver microsomal enzymes. There is some evidence that ranitidine increases the absorption of triazolam, and possibly other benzodiazepines, due to changes in gastric pH, ° although it has been suggested that this effect is negligi-ble. ° Cimetidine has been said to similarly affect the absorption of diazepam and lorazepam. ... 

Intravenous, but not oral, metoclopramide increases the rate of absorption of diazepam and raises its maximum plasma levels. Metoclopramide increases the rate of absorption of zopiclone. 

Diazepam Accelerated absorption of diazepam reported. Transient increase in sedation possible. Monitor the patient and advise that sedation may occur more quickly. 1.21... 

The rates of oral absorption of sedative-hypnotics differ depending on a number of factors, including lipophilicity. For example, the absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate, a prodrug, is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Most of the barbiturates and other older sedative-hypnotics, as well as the newer hypnotics (eszopiclone, zaleplon, zolpidem), are absorbed rapidly into the blood following oral administration. 

The concept of using anionic nanosized emulsion vehicles for enhanced percutaneous absorption of nonsteroidal anti-inflammatory drugs (NSAIDs) and diazepam was clearly proven [189, 190], NSAIDs and diazepam in a nanosized emulsion vehicle also demonstrated noticeable systemic activity. The o/w emulsion was tested for primary irritation in humans in a 48-h trial. Low irritancy and excellent human acceptance were observed, subsequently making the further development of a nanosized emulsion vehicle very attractive. 

When a child has febrile convulsions the decision to embark on continuous prophylaxis is serious for the child, and depends on an assessment of risk factors, e.g. age, nature and duration of the fits. Most children who have febrile convulsions do not develop epilepsy. Prolonged drug therapy, e.g. with phenytoin or phenobarbitone, has been shown to interfere with cognitive development, the effect persisting for months after the drug is withdrawn. Parents may be supplied with a specially formulated solution of diazepam for rectal administration (absorption from a suppository is too slow) for easy and early administration, and advised on managing fever, e.g. use paracetamol at the first hint of fever, and tepid sponging. 

Omeprazole is a proton pump inhibitor. Headache, skin rash, and diarrhea have all been recorded by adverse event registries sufficiently often to suggest causal relations (1). Omeprazole is a modest inhibitor of CYP isoforms. Interactions are less likely than with cimetidine and are probably of no practical importance. However, omeprazole reduces the absorption of drugs that require a low gastric pH (ketoconazole, iron salts, ampicilhn) and can inhibit the hepatic clearance of some drugs (diazepam, warfarin, phenytoin) (2). 

Traditionally, emulsions have been used to deliver oils (castor oil, liquid paraffin) in a palatable form. This is now a minor use, but there is a growing interest in the possibility of improving delivery by the use of lipid o/w emulsions as vehicles for lipophilic dmgs (e.g. diazepam, propofol) for intravenous use. Griseofulvin, presented as an emulsion, exhibits enhanced oral absorption an emulsion of indoxole has superior bioavailability over other oral forms. Medium-chain triglycerides and mono- and diglycerides promote the absorption of ceftriaxone and cefoxitin as well as ciclosporin. 

Direct spectrophotometric analysis of diazepam is applicable provided significant quantities of the hydrolytic contaminants are not present. For material not containing the interfering species the reported maxima at 368 + 2 nm in 0.1N alcoholic sulfuric acid with an absorptivity value of 14.5 may be used for quantitative measurement. The Technicon Autoanalyzer system for dosage form assays of diazepam is based on the direct spectrophotometric assay. 

May cause mild CNS and GI effects and 1 bioavailability of drugs that require acidity for oral absorption (e.g., fluoroquinolones, ketoconazole). Inhibit P450 — >L elimination of diazepam, phenytoin, and warfarin. 

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