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

Iloperidone 2D6 and 3A4 convert iloperidone Ketoconazole a AUC of a single 3-mg Impact of 3A4 inducers
to active metabolites P88 and P95. iloperidone dose and its metabolites P88 not documented.
In 2D6 EM, the t 1/2
of P88 and P95
and P95 by 57%, 55%, and 35%, respectively.
are 26 and 23 hours, respectively; in
Fluoxetine a 3-mg single dose AUC of
PM, 37 and 31 hours, respectively.
iloperidone and P88 metabolite 2-3 fold, and
Only P88 has affinity for D 2
. P95 AUC by 50%.
P88 accounts for 19.5% and 34.0% of Paroxetine a AUC of iloperidone
total exposure in EM and PM,
and P88 metabolite 1.6-fold, and reduces
respectively. P95 has K i
of 3.91 nM
P95 AUC by 50%. Paroxetine (8-12 mg
for 5HT 2A
and 4.7 nM for α 1A
,
twice daily) a steady state C max
of iloperidone
and accounts for 48% and 25% of total
and P88 by 1.6-fold, and b steady state C max
exposure in EM and PM, respectively.
of P95 by 50%. Combined use a steady state
C max
of iloperidone and P88 by 1.4-fold,
and b steady state C max
of P95 1.4-fold.
Olanzapine Direct glucuronidation or 1A2 Increase in olanzapine C max
following Carbamazepine use
mediated oxidation to fluvoxamine is 54% in female nonsmokers a clearance by
N-desmethylolanzapine (inactive). and 77% in male smokers. The mean 50%. Olanzapine
increase in olanzapine AUC is
C p
lower in smokers
52% and 108%, respectively. (with equal dosing).
Paliperidone 59% excreted unchanged in urine, Unlikely to have much of an effect. Carbamazepine use
32% excreted as metabolites. b steady state
Phase 2 metabolism accounts C max
and AUC by 37%.
for no more than 10%.
Quetiapine 3A4 mediated sulfoxidation to active Ketoconazole (200 mg once daily for 4 days), Phenytoin increases
metabolite norquetiapine, t 1/2
≈ 12 hours. b oral clearance of quetiapine by 84%, clearance 5-fold.
Steady state mean C max
and AUC of resulting in a 335% a in maximum C p
.
norquetiapine are ~25% and ~50% of
that for quetiapine.
Risperidone 2D6 converts risperidone to active Fluoxetine and paroxetine a risperidone In a drug interaction study
metabolite 9-OH risperidone. concentration ~ 2.5 fold and 3-9 fold, of risperidone 6 mg/day ×
In 2D6 PMs, half-lives are: risperidone, respectively. Fluoxetine did not affect 9-OH 3 weeks, followed by
20 hours; 9-OH risperidone, 30 hours risperidone conc., but paroxetine lowered 3 weeks of carbamazepine,
9-OH risperidone (13%). Net effect: 2D6
concentration of active
inhibition a levels of active moiety up to 75%. moieties (risperidone +
9-OH risperidone) was
decreased 50%.
(Continued)
CHAPTER 16
PHARMACOTHERAPY OF PSYCHOSIS AND MANIA
433