Enzyme Inducing Effects of Phenobarbital on Nitrazepam Metabolism in Dogs

Abstract

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.