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Monitoring chlordiazepoxide therapy
Because chlordiazepoxide has a wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated in all patients
Chlordiazepoxide (Librium) is a benzodiazepine widely used in the treatment of anxiety, alcohol withdrawal symptoms, and as a premedication for anesthesia. The mechanism of action of all benzodiazepines remains unclear. However, it is known that benzodiazepines facilitate gamma-amino butyric acid (GABA)-mediated neurotransmission in the brain. Benzodiazepines most likely facilitate the inhibitory presynaptic or postsynaptic reactions of GABA.
Chlordiazepoxide is metabolized to long-acting metabolites in the liver to the active metabolite nordiazepam (desmethyldiazepam) and the clearance of the drug is reduced considerably in the elderly and in patients with hepatic disease.
Therapeutic assessment should include measurement of both the parent drug (chlordiazepoxide) and the active metabolite (nordiazepam).
Chlordiazepoxide: 400-3,000 ng/mL
Nordiazepam: 100-500 ng/mL
A therapeutic dose will yield a serum concentration of 1,000 to 3,000 ng/mL.
Toxic concentration: >5,000 ng/mL
The specimen must be protected from light.
1. Langman, LJ, Bechtel L, Holstege CP, Chapter 35: Clinical Toxicology, In Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. WB Saunders Company, Philadelphia, PA, 2011, pp 1109-1188
2. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Edited by CA Burtis, ER Ashwood, DE Bruns, WB Saunders Company, Philadelphia, PA, 2011, Table 60.2, pp 1109-1188
3. Hiemke C, Baumann P, Bergemann N, et al: AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry 2011;44:195-235