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 Isoform | 1A1 | 1A2 | 2A6 | 2B6 | 2C8 | 2C9 | 2C18 | 2C19 | 2D6 | 2E1 | 2J2 | 3A4 | 3A5 | 3A7 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DHPBI | — | — | — | — | — | — | — | — | — | — | — | 78 (6.5) | <LOQ | 14 (1.5) |
| 5-OH-Pimozide | <LOQ | <LOQ | — | — | — | — | <LOQ | — | 35 (11) | — | <LOQ | 2.4 (0.24) | 2.5 (0.22) | <LOQ |
| 6-OH-Pimozide | <LOQ | <LOQ | — | — | — | — | <LOQ | — | 5.8 (1.2) | — | <LOQ | 1.7 (0.33) | 1.4 (0.16) | <LOQ |
LOQ, limit of quantification. 5-OH, 5-hydroxy. 6-OH, 6-hydroxy.