Cilobamine

Charles River CD (male, 150-210 g)^[1]

3 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg; 300 mg/kg; 100 mg/kg (time-course analysis)

p.o.; daily; 4 days; daily; up to 4 days (time-course analysis)

Showed no significant changes in ethylmorphine N-demethylase activity, aniline hydroxylase activity, cytochrome P-450 content, relative liver weight, or recoverable microsomal protein compared to controls at 3 mg/kg.
Significantly increased ethylmorphine N-demethylase activity; showed no significant changes in aniline hydroxylase activity, cytochrome P-450 content, relative liver weight, or recoverable microsomal protein compared to controls at 10 mg/kg.
Significantly increased ethylmorphine N-demethylase and aniline hydroxylase activities; showed no significant changes in cytochrome P-450 content or relative liver weight; decreased recoverable microsomal protein compared to controls at 30 mg/kg.
Significantly increased ethylmorphine N-demethylase activity (8.43 nmol HCHO/min/mg microsomal protein), aniline hydroxylase activity (25.94 nmol p-aminophenol/hr/mg microsomal protein), cytochrome P-450 content (0.96 nmol/mg microsomal protein), and relative liver weight (5.25 g/100 g body weight; control: 4.40 g/100 g body weight) compared to controls; showed no change in recoverable microsomal protein compared to controls at 100 mg/kg.
Revealed prominent hypertrophy of the smooth endoplasmic reticulum in hepatocytes at 100 mg/kg.
Showed ethylmorphine N-demethylase activity peaked after 3 doses, aniline hydroxylase activity peaked after 2 doses, and cytochrome P-450 content plateaued after 2 doses, with slight declines in enzyme activities after subsequent doses during time-course analysis at 100 mg/kg.
Significantly increased ethylmorphine N-demethylase activity, aniline hydroxylase activity, cytochrome P-450 content, relative liver weight (5.63 g/100 g body weight), and recoverable microsomal protein (34.97 mg/g liver wet weight) compared to controls at 300 mg/kg.

Charles River CD (female, 150-210 g)^[1]

100 mg/kg

p.o.; daily; 4 days

Significantly increased ethylmorphine N-demethylase activity (3.35 nmol HCHO/min/mg microsomal protein), aniline hydroxylase activity (16.39 nmol p-aminophenol/hr/mg microsomal protein), cytochrome P-450 content (0.67 nmol/mg microsomal protein), and relative liver weight (4.06 g/100 g body weight) compared to controls.
Showed no change in recoverable microsomal protein compared to controls.