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Pharmacology of drugs in saliva , Benzodiazepines

المؤلف:  Sue Jickells , Adam Negrusz (Editors)

المصدر:  Clarkes Analytical Forensic Toxicology

الجزء والصفحة:  179

2026-10-10

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Pharmacology of drugs in saliva

Benzodiazepines

Benzodiazepines have an unfavourable saliva: plasma ratio (S/P 0.01–0.08) because of the acidic pKa values and a high percentage protein binding in plasma (95–99%); sensitive methods must therefore be used to detect benzodiazepines in saliva (Tjaden et al. 1980). Lucek and Dixon (1980) reported a mean saliva: plasma ratio for chlordiazepoxide of 0.027 ± 0.011. Saliva levels were found to be equal to the concentration of unbound drug in plasma. Diazepam (pKa 3.3) and its metabolites are found in saliva at concentrations of 2–5 lg/L with a saliva: plasma ratio of 0.02 (Giles et al. 1977, 1981; Dixon and Crews 1978). Giles et al. (1980) reported saliva desmethyldiazepam levels in patients who received chronic diazepam therapy. Hallstrom et al. (1980) reported a saliva: plasma ratio of 0.016 ±0.003 for diazepam and 0.029 ±0.01 for nordiazepam in chronic diazepam users. DeGier et al. (1980) reported saliva: plasma ratios of 0.017 ±0.003 for diazepam, but failed to predict plasma free diazepam levels accurately from saliva diazepam concentrations.

Kangas et al. (1979) and Hart et al. (1987) reported that saliva concentrations of nitrazepam were considerably lower than the protein-unbound fraction in serum and that monitoring of saliva nitrazepam was of no clinical value. However, Hart et al. (1988) reported that while diazepam, nordiazepam and clonazepam are stable in saliva, nitrazepam is unstable in saliva and is rapidly converted into 7-aminonitrazepam on standing in saliva at room temperature. Samyn et al. (2002b) reported the detection of flunitrazepam and 7-aminoflunitrazepam in oral fluid using chemical-ionisation GC-MS. Maximum concentrations were reached 2–4 hours after dosing. Flunitrazepam and its metabolites were not stable in oral fluid specimens, even after treatment with sodium fluoride and refrigeration.

Studies of the effect of benzodiazepines on psychomotor performance and driving performance have compared saliva and plasma concentrations (DeGier et al. 1981; Linnoila et al. 1983; Jansen et al. 1988). Results indicate a good correlation between saliva and plasma concentrations, but poor correlation with psychomotor impairment.