DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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SECTION II
NEUROPHARMACOLOGY
Table 16–3
Metabolism of Common Antipsychotic Drugs
AGENT METABOLIC PATHWAYS EFFECT OF CYP INHIBITION EFFECT OF CYP INDUCTION
Atypical Antipsychotic Agents
Aripiprazole 2D6 and 3A4 convert aripiprazole to 2D6 PMs experience 80% a in aripiprazole 3A4 induction
active metabolite dehydro-aripiprazole. AUC, and 30% b in metabolite AUC (net effect b maximum
Metabolite has longer t 1/2
is 60% a in AUC for active moiety). Aripiprazole concentration and
(75 vs. 94 hours) and represents t 1/2
≈ 146 hrs in PM. AUC of aripiprazole
40% of AUC at steady state. 2D6 inhibitors a aripiprazole AUC by and metabolite by 70%.
112% and b metabolite AUC by 35%.
Ketoconazole (a potent 3A4 inhibitor)
with a 15-mg single dose of aripiprazole
a the AUC of aripiprazole and its active
metabolite by 63% and 77%, respectively.
Asenapine Primarily glucuronidation (UGT 1A4), Fluvoxamine, 25 mg twice daily for 8 days, Smoking had no effect
and limited oxidation via CYP 1A2, a C max
by 13% and AUC 29%. on clearance or other
and to a lesser extent 2D6 and 3A4. Paroxetine b both C max
and AUC by kinetic parameters.
No active metabolites. 13%. Valproate, a UGT 1A4 inhibitor, Carbamazepine b
a C max
2%, and b AUC 1%.
both C max
and AUC
by 16%.
Clozapine Multiple enzymes convert clozapine to Fluvoxamine a C p
5-10 fold. 2D6 inhibition Loss of smoking-related
active metabolite N-desmethylclozapine. may a levels as much as 100%. 1A2 induction a
The mean contributions of CYPs 1A2, serum levels by 50%.
2C19, 3A4, 2C9, and 2D6 are 30%, Carbamazepine
24%, 22%, 12%, and 6%, respectively. b clozapine
CYP1A2 is the most important form
levels on average
at low concentrations, which is in by 50%.
agreement with clinical findings.