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ABCB1 polymorphisms...
ABCB1 polymorphisms influence steady-state plasma levels of 9-hydroxyrisperidone and risperidone active moiety
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- Gunes, Arzu (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Pharmacogenetics
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Spina, Edoardo (författare)
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- Dahl, Marja-Liisa (författare)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinska vetenskaper,Pharmacogenetics
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- Scordo, Maria Gabriella (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Pharmacogenetics
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(creator_code:org_t)
- 2008
- 2008
- Engelska.
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Ingår i: Therapeutic Drug Monitoring. - 0163-4356 .- 1536-3694. ; 30:5, s. 628-633
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Risperidone is metabolized to its active metabolite, 9-hydroxy risperidone, mainly by the cytochrome P450 enzymes CYP2D6 and 3A4. Its antipsychotic effect is assumed to be related to the active moiety, that is, the sum of risperidone and 9-hydroxyrisperidone. Both risperidone and 9-hydroxyrisperidone are substrates of P-glycoprotein (P-gp), a transport protein involved in drug absorption, distribution, and elimination. The aim of the present study was to evaluate the influence of polymorphisrns in genes encoding CYP3A5 and P-gp (ABCB1) on the steady-state plasma levels of risperidone, 9-hydroxyrisperidone, and the active moiety, taking CYP2D6 genotype status into account. Forty-six white patients with schizophrenia treated with risperidone (1-10 mg/d) in monotherapy for 4-6 weeks were genotyped, and their plasma concentrations of risperidone and 9-hydroxyrisperidone were measured. Dose-corrected plasma concentrations (C/D) of risperidone, 9-hydroxyrisperidone, and active moiety showed up to 68-, 9-, and 10-fold interindividual variation, respectively. Six patients carried 1 CYP3A5*1 allele and therefore were likely to express the CYP3A5 enzyme. The CYP3A5 genotype did not influence risperidone, 9-hydroxyrisperidone, or active moiety C/Ds. The CYP2D6 genotype in these 46 patients was again associated with risperidone C/D (P = 0.001) but not with 9-hydroxyrisperidone C/D or active moiety C/D, as previously shown by our group in 37 of these patients. Patients homozygous for the ABCB1 3435T/2677T/1236T haplotype had significantly lower C/Ds of 9-hydroxyrisperidone (P = 0.026) and active moiety (P = 0.028) than patients carrying other ABCB1 genotypes. In conclusion, our results confirmed the significant effect of CYP2D6 genotype oil the steady-state plasma levels of risperidone and showed that ABCB1 polymorphisins have a moderate effect oil those of 9-hydroxyrisperidone and the active moiety.
Nyckelord
- risperidone
- 9-hydroxyrisperidone
- ABCB1
- CYP3A4
- CYP3A5
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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