The metabolism of trifluoperazine (TFP) exhibits atypical kinetic behavior in both human liver microsomes (HLMs) and monkey liver microsomes (MyLM)

Glucuronidation reaction of trifluoperazine (TFP) is a typical probe reaction to phenotype the activity of UDP-glucuronosyltransferase 1A4. The present study aims to compare the metabolic behavior of TFP in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. In vitro human liver microsome incubation system was used. The Eadie–Hofstee plot was used to determine the kinetic type. The results showed that the data for human liver microsomes (HLMs) and monkey liver microsomes (MyLMs)-catalyzed glucuronidation were best fit to the substrate inhibition model. For the metabolism of TFP in HLMs, the kinetic parameters were calculated to be 40 ± 5 and 140 ± 20 μM for K m and K si values, respectively. For the MyLM-mediated metabolism of TFP, the K m and K si values were calculated to be 108 ± 10 and 250 ± 30 μM, respectively. The same metabolic kinetic type and different kinetic parameters were demonstrated for the metabolism of TFP between HLMs and MyLMs. All these data were helpful for understanding the metabolism difference of TFP between human and monkey.