Enzyme inducing effects of phenobarbital on nitrazepam metabolism in dogs

A 6-day peroral phenobarbital treatment of beagle dogs decreased clearly and significantly the mean AUC (1252 +/- 270 ng/ml/hr) of a single peroral dose of nitrazepam (1.5 mg/kg), as a sign of enzyme induction to one third (428 +/- 37 ng/ml/hr P < 0.05) in plasma and the concentration maximum (Cmax) (301 +/- 62 ng/ml/hr) to one third (110 +/- 15 ng/ml/hr, P < 0.05), respectively. The mean Kel, 0.36 +/- 0.04, increased to 0.54 +/- 0.04 (P < 0.05), respectively. An 11-day phenobarbital treatment decreased the mean AUC of nitrazepam further to one sixth (197 +/- 41 ng/ml/hr, P < 0.01) and the Cmax to one fifth (65 +/- 10 ng/ml/hr, P < 0.01), while the mean Kel increased from 0.36 +/- 0.04 to 0.65 +/- 0.02 (P < 0.001). The 12- day peroral nitrazepam treatment showed no sign of autoinduction as a single daily dose. The mean AUC of a single nitrazepam dose of the 1st day, 1290 +/- 256 ng/ml/hr increased after the 24-day nitrazepam treatment, to 3617 +/- 202 ng/ml/hr and after the 61-day treatment to 3379 +/- 321 ng/ml/hr. The mean maximum concentration (Cmax), 343 +/- 69 ng/ml/hr, increased to 727 +/- 52 ng/ml/hr, respectively.