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Pharmacokinetics of clonazepam in the dog

, : Pharmacokinetics of clonazepam in the dog. Archives Internationales de Pharmacodynamie et de Therapie 268(2): 180-193

After i.v. administration of 0.2 mg/kg clonazepam to dogs, plasma concentrations followed partly a biexponential and partly a monoexponential decline, the terminal elimination half-life (t0.5 beta or t0.5) being 1.4 +/- 0.3 hr. Over the dose range from 0.1 to 0.5 mg/kg the elimination rate was dose-dependent. At the highest dose level, one dog showed signs of a saturation kinetics. After oral administration absorption was rapid, but bioavailability poor and highly variable (20-60%). In spite of the high elimination rate in the single dose studies, clonazepam plasma concentrations in the range known as "therapeutic" in man could be maintained in subacute studies (1 week) by dosing 0.5 mg/kg b.i.d. or t.i.d. This is most likely explained by a saturation of metabolic inactivation and makes the dog a useful model for man when the drug is given continuously. Protein binding averaged 82% and is thus similar to man. Clonazepam passed the blood/CSF barrier rapidly (P = 0.217 min-1) so that steady state conditions were reached within 10-20 min.


PMID: 6732363

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