Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6

M. Desai, J. E. Tanus-Santos, L. Li, J. C. Gorski, M. Arefayene, Yunlong Liu, Zeruesenay Desta, D. A. Flockhart

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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 QTc 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 QTc 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 QTc changes from baseline that could be considered clinically important. Although the magnitude of the mean QTc prolongation on haloperidol relative to placebo is relatively small, it may assume significance in the presence of other risk factors for QT prolongation.

Original languageEnglish
Pages (from-to)105-113
Number of pages9
JournalPharmacogenomics Journal
Volume3
Issue number2
DOIs
StatePublished - 2003

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Cytochrome P-450 CYP2D6
Haloperidol
Pharmacokinetics
Placebos
Cross-Over Studies
Half-Life

Keywords

  • CYP2D6
  • Genotype
  • Haloperidol
  • QT

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6. / Desai, M.; Tanus-Santos, J. E.; Li, L.; Gorski, J. C.; Arefayene, M.; Liu, Yunlong; Desta, Zeruesenay; Flockhart, D. A.

In: Pharmacogenomics Journal, Vol. 3, No. 2, 2003, p. 105-113.

Research output: Contribution to journalArticle

Desai, M. ; Tanus-Santos, J. E. ; Li, L. ; Gorski, J. C. ; Arefayene, M. ; Liu, Yunlong ; Desta, Zeruesenay ; Flockhart, D. A. / Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6. In: Pharmacogenomics Journal. 2003 ; Vol. 3, No. 2. pp. 105-113.
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