Effects of CYP2D6 and CYP3A5 genotypes on the plasma concentrations of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients

Rhee Hun Kang, Sun Min Jung, Kyoung Ah Kim, Duk Ki Lee, Hyun Kee Cho, Bong Joo Jung, Yong Ku Kim, Seung Hyun Kim, Changsu Han, Min-Soo Lee, Ji-Young Park

Research output: Contribution to journalArticle

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Abstract

This study was conducted to evaluate the effects of the CYP2D6 and CYP3A5 genotypes on the steady-state plasma levels of risperidone (RIS), 9-hydroxyrisperidone (9-OH-RIS), and the active moiety (RIS plus 9-OH-RIS) in Korean schizophrenic patients. Sixty-four Korean schizophrenic patients were enrolled. CYP2D6 and CYP3A5 genotypes were determined, and the plasma levels of RIS and 9-OH-RIS were measured using high-performance liquid chromatography. The dose-normalized plasma concentrations of RIS, 9-OH-RIS, and the active moiety were compared according to the CYP2D6 and CYP3A5 genotypes. Among the patients, 57 were CYP2D6 extensive metabolizers (EMs; CYP2D6*1/*1,*1/ *10, and*10/*10) and 7 were CYP2D6 poor metabolizers (PMs; CYP2D6*1/*5 and*10/*5). For the CYP3A5 genotype, 30 patients were CYP3A5*1 expressors (*1/*1 [n ≤ 1] and*1/*3 [n ≤ 29]) and 34 patients were CYP3A5 nonexpressors (*3/*3). The plasma levels of RIS (2.03 ng/mL per milligram for EMs vs 5.57 ng/mL per milligram for PMs, P < 0.001) and 9-OH-RIS (5.06 ng/mL per milligram for EMs vs 0.22 ng/mL per milligram for PMs, P < 0.001) were significantly different among CYP2D6 genotype groups, but the CYP2D6 EMs (7.09 ng/mL per milligram) and PMs (5.79 ng/mL per milligram) did not show no difference in the levels of the active moiety (P ≤ 0.470). CYP3A5 nonexpressors exhibited higher plasma concentrations of both RIS and 9-OH-RIS than its expressors. In the case of 9-OH-RIS, CYP3A5 nonexpressors exhibited significantly higher concentrations than CYP3A5 expressors (5.42 vs 3.51 ng/mL per milligram, P ≤ 0.022). In addition, concentrations of the active moiety were also significantly different between the CYP3A5 nonexpressors (8.39 ng/mL per milligram) and expressors (5.30 ng/mL per milligram, P ≤ 0.005). In conclusion, both CYP2D6 and CYP3A5 genotypes affected plasma levels of RIS and 9-OH-RIS, whereas the active moiety levels were influenced only by the CYP3A5 genotype but not by the CYP2D6 genotype.

Original languageEnglish
Pages (from-to)272-277
Number of pages6
JournalJournal of Clinical Psychopharmacology
Volume29
Issue number3
DOIs
Publication statusPublished - 2009 Jun 1

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Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2D6
Risperidone
Genotype
Paliperidone Palmitate
hydroxide ion

Keywords

  • 9-hydroxyrisperidone
  • Cytochrome P450 2D6 (CYP2D6)
  • Cytochrome P450 3A5 (CYP3A5)
  • Pharmacogenetics
  • Risperidone

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Effects of CYP2D6 and CYP3A5 genotypes on the plasma concentrations of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients. / Kang, Rhee Hun; Jung, Sun Min; Kim, Kyoung Ah; Lee, Duk Ki; Cho, Hyun Kee; Jung, Bong Joo; Kim, Yong Ku; Kim, Seung Hyun; Han, Changsu; Lee, Min-Soo; Park, Ji-Young.

In: Journal of Clinical Psychopharmacology, Vol. 29, No. 3, 01.06.2009, p. 272-277.

Research output: Contribution to journalArticle

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T1 - Effects of CYP2D6 and CYP3A5 genotypes on the plasma concentrations of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients

AU - Kang, Rhee Hun

AU - Jung, Sun Min

AU - Kim, Kyoung Ah

AU - Lee, Duk Ki

AU - Cho, Hyun Kee

AU - Jung, Bong Joo

AU - Kim, Yong Ku

AU - Kim, Seung Hyun

AU - Han, Changsu

AU - Lee, Min-Soo

AU - Park, Ji-Young

PY - 2009/6/1

Y1 - 2009/6/1

N2 - This study was conducted to evaluate the effects of the CYP2D6 and CYP3A5 genotypes on the steady-state plasma levels of risperidone (RIS), 9-hydroxyrisperidone (9-OH-RIS), and the active moiety (RIS plus 9-OH-RIS) in Korean schizophrenic patients. Sixty-four Korean schizophrenic patients were enrolled. CYP2D6 and CYP3A5 genotypes were determined, and the plasma levels of RIS and 9-OH-RIS were measured using high-performance liquid chromatography. The dose-normalized plasma concentrations of RIS, 9-OH-RIS, and the active moiety were compared according to the CYP2D6 and CYP3A5 genotypes. Among the patients, 57 were CYP2D6 extensive metabolizers (EMs; CYP2D6*1/*1,*1/ *10, and*10/*10) and 7 were CYP2D6 poor metabolizers (PMs; CYP2D6*1/*5 and*10/*5). For the CYP3A5 genotype, 30 patients were CYP3A5*1 expressors (*1/*1 [n ≤ 1] and*1/*3 [n ≤ 29]) and 34 patients were CYP3A5 nonexpressors (*3/*3). The plasma levels of RIS (2.03 ng/mL per milligram for EMs vs 5.57 ng/mL per milligram for PMs, P < 0.001) and 9-OH-RIS (5.06 ng/mL per milligram for EMs vs 0.22 ng/mL per milligram for PMs, P < 0.001) were significantly different among CYP2D6 genotype groups, but the CYP2D6 EMs (7.09 ng/mL per milligram) and PMs (5.79 ng/mL per milligram) did not show no difference in the levels of the active moiety (P ≤ 0.470). CYP3A5 nonexpressors exhibited higher plasma concentrations of both RIS and 9-OH-RIS than its expressors. In the case of 9-OH-RIS, CYP3A5 nonexpressors exhibited significantly higher concentrations than CYP3A5 expressors (5.42 vs 3.51 ng/mL per milligram, P ≤ 0.022). In addition, concentrations of the active moiety were also significantly different between the CYP3A5 nonexpressors (8.39 ng/mL per milligram) and expressors (5.30 ng/mL per milligram, P ≤ 0.005). In conclusion, both CYP2D6 and CYP3A5 genotypes affected plasma levels of RIS and 9-OH-RIS, whereas the active moiety levels were influenced only by the CYP3A5 genotype but not by the CYP2D6 genotype.

AB - This study was conducted to evaluate the effects of the CYP2D6 and CYP3A5 genotypes on the steady-state plasma levels of risperidone (RIS), 9-hydroxyrisperidone (9-OH-RIS), and the active moiety (RIS plus 9-OH-RIS) in Korean schizophrenic patients. Sixty-four Korean schizophrenic patients were enrolled. CYP2D6 and CYP3A5 genotypes were determined, and the plasma levels of RIS and 9-OH-RIS were measured using high-performance liquid chromatography. The dose-normalized plasma concentrations of RIS, 9-OH-RIS, and the active moiety were compared according to the CYP2D6 and CYP3A5 genotypes. Among the patients, 57 were CYP2D6 extensive metabolizers (EMs; CYP2D6*1/*1,*1/ *10, and*10/*10) and 7 were CYP2D6 poor metabolizers (PMs; CYP2D6*1/*5 and*10/*5). For the CYP3A5 genotype, 30 patients were CYP3A5*1 expressors (*1/*1 [n ≤ 1] and*1/*3 [n ≤ 29]) and 34 patients were CYP3A5 nonexpressors (*3/*3). The plasma levels of RIS (2.03 ng/mL per milligram for EMs vs 5.57 ng/mL per milligram for PMs, P < 0.001) and 9-OH-RIS (5.06 ng/mL per milligram for EMs vs 0.22 ng/mL per milligram for PMs, P < 0.001) were significantly different among CYP2D6 genotype groups, but the CYP2D6 EMs (7.09 ng/mL per milligram) and PMs (5.79 ng/mL per milligram) did not show no difference in the levels of the active moiety (P ≤ 0.470). CYP3A5 nonexpressors exhibited higher plasma concentrations of both RIS and 9-OH-RIS than its expressors. In the case of 9-OH-RIS, CYP3A5 nonexpressors exhibited significantly higher concentrations than CYP3A5 expressors (5.42 vs 3.51 ng/mL per milligram, P ≤ 0.022). In addition, concentrations of the active moiety were also significantly different between the CYP3A5 nonexpressors (8.39 ng/mL per milligram) and expressors (5.30 ng/mL per milligram, P ≤ 0.005). In conclusion, both CYP2D6 and CYP3A5 genotypes affected plasma levels of RIS and 9-OH-RIS, whereas the active moiety levels were influenced only by the CYP3A5 genotype but not by the CYP2D6 genotype.

KW - 9-hydroxyrisperidone

KW - Cytochrome P450 2D6 (CYP2D6)

KW - Cytochrome P450 3A5 (CYP3A5)

KW - Pharmacogenetics

KW - Risperidone

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