Perphenazine Tablets

CLINICAL PHARMACOLOGY

Pharmacokinetics

Following oral administration of perphenazine (perphenazine) tablets, mean peak plasma perphenazine (perphenazine) concentrations were observed between 1 to 3 hours. The plasma elimination half-life of perphenazine (perphenazine) was independent of dose and ranged between 9 and 12 hours. In a study in which normal volunteers (n=12) received perphenazine (perphenazine) 4 mg q8h for 5 days, steady-state concentrations of perphenazine (perphenazine) were reached within 72 hours. Mean (%CV) Cmax and Cmin values for perphenazine and 7 hydroxyperphenazine (perphenazine) at steady-state are listed below:

Parameter Perphenazine 7-Hydroxyperphenazine
Cmax (pg/mL) 984 (43) 509 (25)
Cmin (pg/mL) 442 (76) 350 (56)

Peak 7-hydroxyperphenazine (perphenazine) concentrations were observed between 2 to 4 hours with a terminal phase half-life ranging between 9.9 to 18.8 hours. Perphenazine (perphenazine) is extensively metabolized in the liver to a number of metabolites by sulfoxidation, hydroxylation, dealkylation, and glucuronidation. The pharmacokinetics of perphenazine (perphenazine) covary with the hydroxylation of debrisoquine which is mediated by cytochrome P450 2D6 (CYP 2D6) and thus is subject to genetic polymorphism – i.e., 7% to 10% of Caucasians and a low percentage of Asians have little or no activity and are called "poor metabolizers." Poor metabolizers of CYP 2D6 will metabolize perphenazine (perphenazine) more slowly and will experience higher concentrations compared with normal or "extensive" metabolizers.

Last reviewed on RxList: 10/21/2008
This monograph has been modified to include the generic and brand name in many instances.

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