The Role Of Cyp2d6, Cyp3a4/5, And Abcb1 Polymorphisms In Patients Using Long-Acting Injectable Risperidone

Ganoci, Lana; Lovrić, Mila; Živković, Maja; Šagud, Marina; Domjanović, Iva Klarica; Božina, Nada

doi:10.1016/j.clinthera.2016.07.110

Cited by 5 publications

(4 citation statements)

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“…CYP3A5 non-expressors exhibited higher plasma concentrations of both risperidone and 9-hydroxyrisperidone and a higher active moiety than its expressors ( Kang et al, 2009 ). However, two different candidate gene studies did not find differences in concentrations of risperidone, 9-hydroxyrisperidone and the active moiety regarding the CYP3A phenotype ( Vandenberghe et al, 2015 ; Ganoci et al, 2016 ). Further studies are needed to estimate the influence of CYP3A phenotype on risperidone pharmacokinetics ( Table 4 ).…”

Section: Pharmacogenetics Of Olanzapine Aripiprazole and Risperidonementioning

confidence: 88%

Genetic Polymorphisms Associated With the Pharmacokinetics, Pharmacodynamics and Adverse Effects of Olanzapine, Aripiprazole and Risperidone

et al. 2021

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Olanzapine, aripiprazole and risperidone are atypical antipsychotics or neuroleptics widely used for schizophrenia treatment. They induce various adverse drug reactions depending on their mechanisms of action: metabolic effects, such as weight gain and alterations of glucose and lipid metabolism; hyperprolactinemia and extrapyramidal effects, such as tremor, akathisia, dystonia, anxiety and distress. In this review, we listed polymorphisms associated with individual response variability to olanzapine, aripiprazole and risperidone. Olanzapine is mainly metabolized by cytochrome P450 enzymes, CYP1A2 and CYP2D6, whereas aripiprazole and risperidone metabolism is mainly mediated by CYP2D6 and CYP3A4. Polymorphisms in these genes and other enzymes and transporters, such as enzymes from the uridine 5'-diphospho-glucuronosyltransferase (UGT) family and ATP-binding cassette sub-family B member 1 (ABCB1), are associated to differences in pharmacokinetics. The three antipsychotics act on dopamine and serotonin receptors, among others, and several studies found associations between polymorphisms in these genes and variations in the incidence of adverse effects and in the response to the drug. Since olanzapine is metabolized by CYP1A2, a lower starting dose should be considered in patients treated with fluvoxamine or other CYP1A2 inhibitors. Regarding aripiprazole, a reduced dose should be administered in CYP2D6 poor metabolizers (PMs). Additionally, a reduction to a quarter of the normal dose is recommended if the patient is treated with concomitant CYP3A4 inhibitors. Risperidone dosage should be reduced for CYP2D6 PMs and titrated for CYPD6 ultrarapid metabolizers (UMs). Moreover, risperidone dose should be evaluated when a CYP2D6, CYP3A4 or ABCB1 inhibitor is administered concomitantly.

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Section: Pharmacogenetics Of Olanzapine Aripiprazole and Risperidonementioning

confidence: 88%

Genetic Polymorphisms Associated With the Pharmacokinetics, Pharmacodynamics and Adverse Effects of Olanzapine, Aripiprazole and Risperidone

et al. 2021

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“…Consequently, there was an over-representation of adverse events and discontinuation of treatment for PMs. Conversely, a similar study with Croatian psychiatric patients receiving RIS injections found individuals classified as UM with concentrations of RIS active moiety (RIS + 9-OH-RIS) not reaching the threshold recommended for therapeutic range (Ganoci et al, 2016). Kaur et al (2017) reported an association between the CYP2D6 * 4 PM haplotype and treatment dropout due to poor response.…”

Section: Risperidonementioning

confidence: 97%

How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?

et al. 2020

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Many genetic variants in drug metabolizing enzymes and transporters have been shown to be relevant for treating psychiatric disorders. Associations are strong enough to feature on drug labels and for prescribing guidelines based on such data. A range of commercial tests are available; however, there is variability in included genetic variants, methodology, and interpretation. We herein provide relevant background for understanding clinical associations with specific variants, other factors that are relevant to consider when interpreting such data (such as age, gender, drug–drug interactions), and summarize the data relevant to clinical utility of pharmacogenetic testing in psychiatry and the available prescribing guidelines. We also highlight areas for future research focus in this field.

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“…This range is derived exclusively from orally given risperidone studies, extrapolating this range to patients treated with long-acting formulations, which has not yet been extensively studied. Two different studies used this AGNP range [ 35 , 36 ] but the other two studies differ and propose other ranges for LAI risperidone [ 37 , 38 ]. De Leon et al [ 39 ] proposed an updated therapeutic range (20–30 ng/mL) for LAI risperidone as a consequence of the prolonged absorption of LAI formulations and the reduction in the administration frequency, which leads to less oscillations at steady-state conditions.…”

Section: Long-acting Risperidonementioning

confidence: 99%

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

et al. 2021

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Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of life.

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The Role Of Cyp2d6, Cyp3a4/5, And Abcb1 Polymorphisms In Patients Using Long-Acting Injectable Risperidone

Cited by 5 publications

References 0 publications

Genetic Polymorphisms Associated With the Pharmacokinetics, Pharmacodynamics and Adverse Effects of Olanzapine, Aripiprazole and Risperidone

Genetic Polymorphisms Associated With the Pharmacokinetics, Pharmacodynamics and Adverse Effects of Olanzapine, Aripiprazole and Risperidone

How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

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