Korean J Biol Psychiatry.  2011 May;18(2):95-100.

The Effect of CYP2D6/3A5 Genotypes on Plasma Concentrations of Haloperidol after Adjunctive Treatment of Aripiprazole

• Shim JC
• Ahn JM
• Jung DU
• Kong BG
• Kang JW
• Liu KH
• Shin JG

Abstract

OBJECTIVES
To evaluate the drug interactions between aripiprazole and haloperidol, authors investigated plasma concentrations of those drugs by genotypes. METHOD: Fifty six patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders 4th edition diagnosis of schizophrenia were enrolled in this eight-week, double blind, placebo-controlled study. Twenty-eight patients received adjunctive aripiprazole treatment and twenty-eight patients received placebo while being maintained on haloperidol treatment. Aripiprazole was dosed at 15 mg/day for the first 4 weeks, and then 30 mg for the next 4 weeks. The haloperidol dose remained fixed throughout the study. Plasma concentrations of haloperidol and aripiprazole were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, week 1, 2, 4 and 8. *1, *5, and *10 B alleles of CYP2D6 and *1 and *3 alleles of CYP3A5 were determined. The Student's T-test, Pearson's Chi-square test, Wilcoxon Rank Sum test and Logistic Regression analysis were used for data analysis. All tests were two-tailed and significance was defined as an alpha < 0.05.
RESULTS
In the frequency of CYP2D6 genotype, *1/*10 B type was most frequent (36.5%) and *1/*1 (30.8%), *10B/*10B (17.3%) types followed. In the frequency of CYP3A5 genotype, *3/*3 type was found in 63.5% of subjects, and *1/*3 type and *1/*1 were 30.8% and 5.8% respectively. The plasma levels of haloperidol and its metabolites did not demonstrate significant time effects and time-group interactions after adjunctive treatment of aripiprazole. The genotypes of CYP2D6 and 3A5 did not affect the plasma concentration of haloperidol in this trial. No serious adverse event was found after adding aripiprazole to haloperidol.
CONCLUSION
No significant drug interaction was found between haloperidol and aripiprazole. Genotypes of CYP2D6 and 3A5 did not affect the concentration of haloperidol after adding aripiprazole.

Keyword

Aripiprazole; Haloperidol; Drug interaction; Cytochrome P450

MeSH Terms

Alleles
Cytochrome P-450 CYP2D6
Cytochrome P-450 Enzyme System
Diagnostic and Statistical Manual of Mental Disorders
Aripiprazole
Drug Interactions
Genotype
Haloperidol
Humans
Logistic Models
Mass Spectrometry
Piperazines
Plasma
Quinolones
Schizophrenia
Statistics as Topic
Cytochrome P-450 CYP2D6
Cytochrome P-450 Enzyme System
Haloperidol
Piperazines
Quinolones