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Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6
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Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6
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Journal Article
Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6
2003
Overview
ABSTRACT
We studied the pharmacokinetics and QT interval pharmacodynamics of a single 10 mg dose of oral haloperidol in a randomized, double-blind, placebo-controlled, crossover trial of healthy poor (PMs) and extensive (EMs) metabolizers of
CYP2D6
. There was a statistically significant greater mean QT
c
on haloperidol (421.6±20.1 ms) than on placebo (408.4±18.5 ms,
P
=0.0053) occurring 10 h post haloperidol/placebo administration. Men and women had similar ranges of QT
c
changes from placebo. Despite a statistically significant greater mean elimination half-life (19.1±3.6
vs
12.9±4.0 h,
P
=0.04) and lower mean apparent oral clearance (12.8±4.1
vs
27.0±11.3 ml/min/kg,
P
=0.02) of haloperidol in
CYP2D6
PMs than in EMs, this exposure change did not translate into marked QT
c
changes from baseline that could be considered clinically important. Although the magnitude of the mean QT
c
prolongation on haloperidol relative to placebo is relatively small, it may assume significance in the presence of other risk factors for QT prolongation.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Alleles
/ Antipsychotic Agents - adverse effects
/ Antipsychotic Agents - pharmacokinetics
/ Antipsychotic Agents - pharmacology
/ Biomedical and Life Sciences
/ Cytochrome P-450 CYP2D6 - genetics
/ Electrocardiography - drug effects
/ Female
/ Genotype
/ Haloperidol - adverse effects
/ Haloperidol - pharmacokinetics
/ Humans
/ Male
/ Oncology
