Modification by phenobarbital of chlorphentermine-induced changes in lung morphology and drug-metabolizing enzymes in newborn rats.

Treatment of newborn rat pups with 60 mg/kg.d chlorphentermine for 7 d produced on accumulation of alveolar foam cells accompanied by an increase in relative pulmonary tissue weight. In contrast, administration of 20 mg/kg.d for 1 wk did not markedly alter lung ultrastructure or weight in newborns. Both doses of chlorphentermine elevated the activity of pulmonary aminopyrine N-demethylase but not that of aniline hydroxylase. The increase in relative liver weight was associated with stimulation of the activities of aniline hydroxylase and aminopyrine N-demethylase in newborns administered either chlorphentermine dose. Phenobarbital treatment produced an increase in relative liver weight accompanied by elevated activities of pulmonary aminopyrine N-demethylase and hepatic aniline hydroxylase and aminopyrine N-demethylase. Simultaneous barbiturate and chlorphentermine administration produced stimulation in liver enzymes to the same extent as phenobarbital alone. In contrast, phenobarbital potentiated the chlorphentermine-induced rise in pulmonary aminopyrine N-demethylase. In the case of 60 mg/kg chlorphentermine and barbiturate, the observed potentiation of lung enzyme activity was associated with a reduction in the number of alveolar foam cells. The results suggest that chlorphentermine and phenobarbital stimulate drug-metabolizing enzyme in lung and liver of newborn rats and that phenobarbital may provide protection against phospholipidosis through stimulation of pulmonary, drug-metabolizing enzymes.