Identification of metabolic pathways of pindolol and fluperlapine in adult human hepatocyte cultures

Abstract

1. Adult human hepatocytes were obtained from a normal donor and a barbiturate-overdose fatality and maintained either in pure culture or in co-culture with rat liver epithelial cells. At varying times of culture, metabolic pathways of pindolol and fluperlapine, two drugs which are transformed at different rates and routes in man and rat, were determined after a 24 h incubation.

2. In both culture conditions, human hepatocytes remained able to form the major urinary metabolites of pindolol and fluperlapine, including oxidized products, glucuronide and sulphate conjugates over the whole period studied (i.e. 5 and 21 days in pure and co-culture respectively).

3. Fluperlapine which has the higher first pass in man and animals was found to be metabolized in vitro more quickly than pindolol.

4. Some qualitative and quantitative differences were found between normal and drug-altered human hepatocytes, indicating that in vivo environmental factors may greatly influence metabolic properties of these cells even after several days in culture.