Pharmacokinetics of chlordiazepoxide and metabolites following single and multiple oral doses.

Article Details

Citation

Greenblatt DJ, Shader RI, Franke K, Harmatz JS

Pharmacokinetics of chlordiazepoxide and metabolites following single and multiple oral doses.

Int J Clin Pharmacol Biopharm. 1978 Oct;16(10):486-93.

PubMed ID
700911 [ View in PubMed
]
Abstract

Three healthy volunteers (2 male and one female) participated in single- and multiple-dose pharmacokinetic studies of oral chlordiazepoxide (CDX) hydrochloride. Following single 50-mg oral doses of CDX.HCl, absorption and elimination proceeded as apparent first-order processes. Values of absorption half-life were: 14.5, 189, and 18.9 minutes; elimination half-lives were: 7.6, 9.8, and 12.6 hours. Disappearance of CDX was mirrored by appearance of its first active metabolite, desmethylchlordiazepoxide (DMCDX). During once-daily ingestion of 50 mg of CDX.HCl, observed values of CDX accumulation half-life (0.0, 5.8, and 52.5 hours) differed substantially from values predicted based upon the single-dose study; pre-dose steady-state CDX blood concentrations also differed from the predicted values. Accumulation half-lives for the metabolite DMCDX were: 17.7, 9.9, and 15.8 hours. Accumulation in blood of a second active metabolite, demoxepam (DMX), proceeded with half-life values of 21.1, 34.2, and 78.5 hours. Minimum steady-state concentrations of DMCDX and DMX exceeded those of the parent compound. Thus accumulation and persistence of at least two active metabolites during long-term treatment with chlordiazepoxide renders the drug suitable for single-daily dose therapy of anxiety.

DrugBank Data that Cites this Article

Pharmaco-metabolomics
DrugDrug GroupsMetaboliteChangeDescription
ChlordiazepoxideApproved Illicit InvestigationalDemoxepam
increased
Chlordiazepoxide increases the level of Demoxepam in the blood