The effects of flumazenil-precipitated abstinence on the pharmacokinetics of chronic oxazepam in dogs.

The pharmacokinetics of oxazepam was studied in naive dogs and in oxazepam-dependent dogs without and with administered flumazenil (6 mg/kg). Oxazepam is eliminated with a relatively short elimination half life (ca. 150 min) in both acutely and chronically treated dogs. It exhibits only a modest first pass metabolism (ca. 10%) and its bioavailability following oral administration is about 22%. The steady state concentration of oxazepam in chronically treated dogs was lower than was predicted from single dose studies. Flumazenil did not change the rate of absorption or elimination of oxazepam-dependent dogs. The total steady state plasma concentration of oxazepam was significantly reduced by flumazenil administration suggesting a displacement interaction between flumazenil and oxazepam.