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 (continued)
METABOLIC PATHWAYS EFFECT OF CYP INHIBITION EFFECT OF CYP INDUCTION
Atypical Antipsychotic Agents
Ziprasidone 3A4 (~1/3) Concomitant ketoconazole Carbamazepine
Aldehyde Oxidase (~2/3) a AUC by 35% b AUC by 35%.
Typical Antipsychotic Agents
Haloperidol Multiple CYP pathways, particularly Half-life prolonged in CYP 2D6 PMs Carbamazepine and phenytoin
2D6, 3A4, and minor pathway 1A2. Individuals with only one functional a haloperidol clearance
Only active metabolite, reduced 2D6 allele experience 2-fold greater trough ~32%, with b C p
haloperidol (formed by ketone reductase). serum levels, those with no functioning (mean, 47%).
Reduced haloperidol inhibits CYP2D6 alleles 3-4 fold higher. Discontinuation of
and may be re-oxidized to the parent drug.
carbamazepine a C p
Therapeutic serum levels not well
2-3 fold.
defined; 5-20 ng/mL used
as a target for dosing.
Chlorpromazine CYP2D6. Over 10 identified human Case report of fluoxetine-chlorpromazine 3A4/PGP inducers (e.g.,
metabolites, most inactive. interaction, but no serum level data on phenobarbital,
Chlorpromazine is a moderate 2D6 extent of effect. carbamazepine)
inhibitor, and also induces its own
decrease chlorpromazine
metabolism. Levels drop 25-33% levels by ~35%.
during weeks 1-3 of treatment.
Carbamazepine
discontinuation
a C p
(30-80%).
AUC, area under the curve; PM, poor metabolizer; EM, extensive metabolizer; t 1/2
, half life; C p
, plasma concentration; C max
, maximum plasma concentration.
a
May have multiphasic elimination with much longer terminal t 1/2
.