[Metabolic interactions of promethazine (author's transl)]

Owing to enzyme induction, the pretreatment of female Wistar rats with promethazine (Prothazin, Atosil) produces a shortening of the hexobarbital sleeping time, a slight increase in the relative liver weight, an increase in the N-demethylation of aminophenazone, the O-demethylation of codeine phosphate, the O-demethylation of p-nitroanisol, the glucuronidation of p-nitrophenol and the NADPH-cytochrome c reductase activity in the 9.000 g supernatant of liver homogenates. Particularly striking are the strong stimulation of the N-demethylation and the also potentiated [in contrast to the findings obtained with dioxopromethazine (Prothanon)] UDP-glucuronyltransferase activity, whereas the cytochrome P-450 concentration shows a slight trend toward increase, but this is not statistically significant. The findings obtained justify the expectation of drug interactions in case of repeated application of promethazine in the framework of a combined therapy.