Comparison of pimozide metabolite concentrations produced in incubations of recombinant cytochrome P450 isoforms

Recombinant human cytochrome P450 isoforms (2 pmol/ml) were incubated with 2500 nM pimozide for 30 min. Numbers represent the mean (S.D.) from triplicate experiments for the concentrations (nanomolars) of the specific metabolites observed after quenching of incubations. A “—” denotes a cytochrome P450 isoform that was not observed to produce detectable amounts of the listed metabolites. The lower LOQs for this experiment were 1 nM for 5-/6-hydroxypimozide and 5 nM for DHPBI. Experimental conditions were not confirmed to be linear with respect to time.

Cytochrome P450 Isoform1A11A22A62B62C82C92C182C192D62E12J23A43A53A7
DHPBI78 (6.5)<LOQ14 (1.5)
5-OH-Pimozide<LOQ<LOQ<LOQ35 (11)<LOQ2.4 (0.24)2.5 (0.22)<LOQ
6-OH-Pimozide<LOQ<LOQ<LOQ5.8 (1.2)<LOQ1.7 (0.33)1.4 (0.16)<LOQ
  • LOQ, limit of quantification. 5-OH, 5-hydroxy. 6-OH, 6-hydroxy.