Pharmacokinetics of Nitrazepam in Saliva and Serum after a Single Oral Dose

Kangas, Lauri; Allonen, H; Lammintausta, Risto; Salonen, Markku; Pekkarinen, A.

doi:10.1111/j.1600-0773.1979.tb02354.x

Cited by 29 publications

(7 citation statements)

References 25 publications

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“…Studies on the detection of other benzodiazepines in oral fluid also have been reported including chlordiazepoxide, 53 clorazepate, 49 flunitrazepam, 54 midazolam, 55 nitrazepam, 56,57 and oxazepam 51 …”

Section: Drug Interpretationmentioning

confidence: 99%

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Interpretation of Oral Fluid Tests for Drugs of Abuse

Cone¹,

Huestis

2007

Annals of the New York Academy of Sciences

159

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Oral fluid testing for drugs of abuse offers significant advantages over urine as a test matrix. Collection can be performed under direct observation with reduced risk of adulteration and substitution. Drugs generally appear in oral fluid by passive diffusion from blood, but also may be deposited in the oral cavity during oral, smoked, and intranasal administration. Drug metabolites also can be detected in oral fluid. Unlike urine testing, there may be a close correspondence between drug and metabolite concentrations in oral fluid and in blood. Interpretation of oral fluid results for drugs of abuse should be an iterative process whereby one considers the test results in the context of program requirements and a broad scientific knowledge of the many factors involved in determining test outcome. This review delineates many of the chemical and metabolic processes involved in the disposition of drugs and metabolites in oral fluid that are important to the appropriate interpretation of oral fluid tests. Chemical, metabolic, kinetic, and analytic parameters are summarized for selected drugs of abuse, and general guidelines are offered for understanding the significance of oral fluid tests.

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Section: Drug Interpretationmentioning

confidence: 99%

“…52 A significant correlation also was reported for diazepam concentration in oral fluid and CSF. 49 Studies on the detection of other benzodiazepines in oral fluid also have been reported including chlordiazepoxide, 53 clorazepate, 49 flunitrazepam, 54 midazolam, 55 nitrazepam, 56,57 and oxazepam. 51…”

Section: Benzodiazepines Overviewmentioning

confidence: 99%

Interpretation of Oral Fluid Tests for Drugs of Abuse

Cone¹,

Huestis

2007

Annals of the New York Academy of Sciences

159

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“…The oral fluid concentration of diazepam reflects the unbound drug concentration in plasma, making oral fluid a useful drug‐monitoring matrix 68,69 . In addition, oral fluid clobazam and nitrazepam concentrations correlated with those in plasma; however, the correlation for nitrazepam concentrations was found to be time dependent 70 . The stability of nitrazepam in oral fluid has been shown to convert into 7‐aminonitrazepam at room temperature with a conversion rate that is dependent on the composition of the subject's oral fluid 71 .…”

Section: Saliva Therapeutic Drug Management Applied To Drug Classesmentioning

confidence: 99%

The Use of Oral Fluid for Therapeutic Drug Management

Langman

2007

Annals of the New York Academy of Sciences

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One of the underlying tenets of clinical pharmacology is that only free drugs are pharmacologically active. It is thought that only free drugs can cross biological membranes to interact with a given receptor to alter its function, and that drug responses, both efficacious and toxic, are a function of unbound concentrations. The rationale for measuring drugs in oral fluid is that the free fraction of a drug in plasma reaches equilibrium with the drug in saliva. Although reports concerning the appearance of organic solutes in saliva have been in the literature for over 70 years, it has only been in the past 30 years that there has been emphasis on the appearance of drugs. Although many assumptions for drug level monitoring in saliva are made, the primary requisite for salivary monitoring to be useful is a constant or predictable relationship between the drug concentration in saliva and the drug concentration in plasma. Measurement of oral fluid drug levels for the purpose of managing patients and making dosage adjustments may be useful for select drugs or drug classes. However, it does not appear to be useful for the majority of drugs therapeutically monitored. Some work with antipsychotic medications has indicated that although the measurement of drug concentrations themselves may not be useful for dosage adjustment, the ratio of parent drug to metabolite may reflect altered metabolic status due to either pharmacogenetic variation or other clinical conditions. Furthermore, analysis of saliva may provide a cost-effective approach for the screening of large populations.

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“…In another study, concentrations of nitrazepam 20 h after administration of 5 mg were about 0.8 ng/ml in oral fluid and 15 ng/ml in serum [43]. By extrapolating the results for those two studies, the legal limit of 17 ng/ml in blood is expected to correspond to 0.8 ng/ml in oral fluid.…”

Section: Nitrazepammentioning

confidence: 94%

“…Method B: In a study of concentrations of nitrazepam in oral fluid and plasma after administration of 5 mg to 12 healthy volunteers, the mean OF/plasma ratio varied from about 0.04 a few hours after administration to about 0.08 three days after administration [43]. Using 0.06 as mean OF/B ratio, the proposed legal limit corresponds to 1.0 ng/ml in oral fluid.…”

Section: Nitrazepammentioning

confidence: 97%