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Interpretive Handbook

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Test 501030:
Nordiazepam, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Benzodiazepine compounds, of which diazepam is a prototype, are widely used as antianxiety, hypnotic, and muscle relaxant agents. Diazepam (Valium) also is frequently used to treat status epilepticus, which is a state of rapidly recurring convulsive seizures that will not respond immediately to conventional anticonvulsant therapy. Although diazepam has been the benzodiazepine of choice for status epilepticus, recent evidence indicates that other drugs may be more beneficial because they provide longer control of seizures and produce less cardiorespiratory depression. Patients develop tolerance to diazepam, which requires that they be converted to phenobarbital or phenytoin within 24 to 48 hours of seizure control with diazepam.

 

Diazepam is administered intravenously or intramuscularly at a dose of 10 to 20 mg in adults to control recurrent seizures. It is rapidly absorbed, reaching peak plasma concentrations in 1 hour. Drug elimination follows a biphasic pattern with a rapid phase of 2 to 3 hours followed by a slow decay with a half-life of 2 to 8 days. After steady-state concentrations are achieved (in about a week), a half-life of 3 to 4 days is found. Diazepam has a volume of distribution of 1.1 L/kg, a half-life of 48 hours, and is 99% protein bound in serum.

 

Nordiazepam is the major metabolite of diazepam, tranxene, and prazepam, and can be differentiated from other benzodiazepines by gas-liquid chromatography (GLC). Nordiazepam has a blood half-life of 4 to 5 days.

Useful For Suggests clinical disorders or settings where the test may be helpful

Assessing compliance

 

Monitoring for appropriate therapeutic level

 

Assessing toxicity

Interpretation Provides information to assist in interpretation of the test results

For seizures:

Serum concentrations are not usually monitored during early therapy because response to the drug can be monitored clinically as seizure control. If seizures resume despite adequate therapy, another anticonvulsant must be considered.

 

For antianxiety and other uses:

-Therapeutic concentrations of diazepam are 0.2 to 0.8 mcg/mL

-After a normal dose of diazepam, tranxene, or prazepam, nordiazepam concentrations range from 0.4 to 1.2 mcg/mL

-Sedation occurs when the total benzodiazepine concentration is >2.5 mcg/mL

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

No significant cautionary statements.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Therapeutic concentration: 0.2-1.0 mcg/mL

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Reidenberg MM, Levy M, Warner H, et al: Relationship between diazepam dose, plasma level, age, and central nervous system depression. Clin Pharmacol Ther 1978 Apr; 23(4):371-374

2. Kelly RC, Anthony RM, Krent L, et al: Toxicological determination of benzodiazepines in serum: methods and concentrations associated with high-dose intravenous therapy with diazepam. Clin Toxicol 1979 Apr;14(4):445-457