PMID: 7337498Dec 1, 1981Paper

Pharmacokinetics of diazepam in the dog

Archives Internationales De Pharmacodynamie Et De Thérapie
W Löscher, H H Frey

Abstract

After i.v. administration of 2 mg/kg diazepam to dogs, concentrations of unmetabolized drug showed a triexponential decline with an average elimination half-life t0.5(beta) of 3.2 hr. Desmethyldiazepam appeared rapidly in plasma and exceeded diazepam concentrations by far. Elimination half-lives of this metabolite averaged 3.6 hr. Oxazepam reached maximal plasma concentrations in the range of 100 ng/ml after about 2 hr which then declined with a half-life of 5.7 hr. When the sum of the concentrations of diazepam and its active metabolites was plotted against time, the curve could be fitted by an open 2-compartment model, so that one of the apparent 3 compartments in the distribution of diazepam must be assumed to represent first pass demethylation to desmethyldiazepam. After oral administration of the same dose, desmethyldiazepam concentrations exceeded those of diazepam from the first blood sample taken. The share of unmetabolized diazepam in the total area under curve was only 1-3% after oral administration, but 7-21% after i.v. administration. Oral bioavailability was in the range of 74-100%. By continued oral administration of 1 or 2 mg/kg diazepam t.i.d. it was possible to maintain steady state plasma concentrations of 100...Continue Reading

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