INVOLVEMENT OF CYP3A4 AND CYP2D6 IN THE METABOLISM OF HALOPERIDOL

1. Human cytochrome P450 (CYP) isoenzymes expressed in a human cell li ne were used to elucidate their involvement in the metabolism of halop eridol (HAL) 2. It was found that CYP3A4 catalyzes the metabolism of H AL to HAL 1,2,3,6-tetrahydropyridine (HTP). HTP is further metabolized to HAL pyridinium (HP+) by both CYP3A4 and CYP2D6. 3. CYP3A4 and CYP2 D6 are also responsible for the N-dealkylation of HAL, The N-dealkylat ion of reduced HAL (RH) was observed, which is catalyzed by CYP3A4. In addition, CYP3A4 also catalyzes the oxidation of RH back to HAL. 4. T hese results are discussed in terms of the metabolic interactions of H AL with other drugs and how this knowledge may be used to reduce the m ovement disorders induced by HAL.