After a 3-day treatment with T3 the ethylmorphine N-demethylation rate was diminished in 10- to 60-day-old rats, whereas the ethoxycoumarin O-deethylation rate was distinctly enhanced in some age-groups, particularly in 33-day-old rats. P-450 concentration was decreased in young rats and not changed in 60-day-old ones. Phenobarbital administration enhanced the rate of both reactions and P-450 concentration in all age-groups. This treatment significantly attenuated the T3 effects on P-450 concentration and ethylmorphine N-demethylation. beta-Naphthoflavone induced ethoxycoumarin O-deethylation and P-450 concentration in all age-groups. Compared with non-induced animals, the T3 effects on ethoxycoumarin O-deethylation (increase) and ethylmorphine N-demethylation (decrease) were more distinct, whereas P-450 concentration was scarcely influenced by T3. Age-differences in T3 actions were generally diminished by inducers.
The influence of T3 on some cytochrome P-450-dependent biotransformation reactions (ethylmorphine N-demethylation, ethoxycoumarin O-deethylation and ethoxyresorufin O-deethylation) was investigated in rats of different ages. After T3 administrations on 3 consecutive days to rats of different ages, on the 4th day ethylmorphine N-demethylation rate was diminished in all age groups. On the contrary, ethoxyresorufin and ethoxycoumarin O-deethylation rates were considerably enhanced, preferentially in 33-day-old animals. The P-450 concentration was increased to a smaller degree. After T3 treatment on the first 8 days of life long-term effects on ethylmorphine N-demethylation were observed. Low T3 doses accelerated this reaction in 33- and 60-day-old rats. Ethoxycoumarin O-deethylation was not influenced. T3 administrations cannot diminish age-differences in drug metabolism.