The Influence of the CYP3A4*22 Polymorphism and CYP2D6 Polymorphisms on Serum Concentrations of Aripiprazole, Haloperidol, Pimozide, and Risperidone in Psychiatric Patients

Weide, Karen van der; Weide, Jan van der

doi:10.1097/jcp.0000000000000319

Cited by 54 publications

(41 citation statements)

References 59 publications

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“…After removing duplicates, we reviewed the remaining 185 articles in the form of title and abstract; 121 citations were excluded after the title and abstract screen. Subsequently, 55 articles were excluded following a full‐text screen, leaving 10 articles eligible for meta‐analysis . The general characteristics of the included studies are summarized in Table .…”

Section: Resultsmentioning

confidence: 99%

“…The serum level of aripiprazole was significantly lower in EMs than in IMs (EM vs IM pooled SMD: −0.383; 95% CI: −0.735 to −0.031, P = 0.03; Figure B). We next conducted a sensitivity analysis of heterogeneity; when the study by van der Weide and van der Weide was omitted, the observed heterogeneity across the studies was clearly reduced ( I 2 = 0.0%, P Q = 0.60 > 0.5), while the difference in aripiprazole serum levels between CYP2D6 EMs and IMs remained significant (EM vs IM pooled SMD: −0.516; 95% CI: −0.743 to −0.289, P < 0.001).…”

Section: Resultsmentioning

confidence: 99%

“…Original data were collected in the form of “Mean, SD, n,” except for four studies, in which the original data were presented in the form of “median, range, n.” For these, we estimated the mean and variance based on the median, range and size of the sample using the method introduced by Hozo et al…”

Section: Methodsmentioning

confidence: 99%

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Association between aripiprazole pharmacokinetics and CYP2D6 phenotypes: A systematic review and meta-analysis

et al. 2018

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Summary What is known and objective The FDA has provided recommendations for aripiprazole use in CYP2D6 poor metabolizers (PMs); however, PMs make up <1% of the Asian population and no recommendation has been provided for intermediate metabolizers (IMs), who comprise a considerable proportion of the Asian population (64%‐70% occurrence of CYP2D6*10). This study aimed to investigate the characteristics of aripiprazole metabolism in IMs and other phenotypes by conducting the first meta‐analysis of the association among CYP2D6 phenotypes and aripiprazole pharmacokinetics (PK). Methods We searched four electronic databases for studies published through February 2018, investigating the association between aripiprazole and CYP2D6 gene polymorphisms. Gene polymorphism information was extracted, and CYP2D6 phenotypes were determined according to a unified classification standard. The associations between three aripiprazole PK‐related outcomes and CYP2D6 phenotype were analysed. Meta‐analyses were used to compare ultra‐rapid metabolizers (UMs) vs extensive metabolizers (EMs), EMs vs IMs and IMs vs poor metabolizers (PMs) for each outcome. The aripiprazole serum concentration funnel plot and the Egger's and Begg's tests were used to assess publication bias. Results and discussion Altogether, 10 studies were included in this analysis (n = 649). Aripiprazole serum concentration differed significantly between EMs and IMs (EM vs IM pooled SMD: −0.383; 95% CI: −0.735 to −0.031, P = 0.03 < 0.05), but not between IMs and PMs (IM vs PM pooled SMD: −0.425; 95% CI: −0.933 to 0.082, P = 0.10 > 0.05). However, aripiprazole plus dehydroaripiprazole serum level did not significantly differ among EMs, IMs and PMs (EM vs IM pooled SMD: −0.285; 95% CI: −0.724 to 0.154, P = 0.20 > 0.05; IM vs PM pooled SMD: −0.302; 95%CI: −0.810 to 0.205, P = 0.24 > 0.05). Overall, aripiprazole serum level and the sum level of aripiprazole plus dehydroaripiprazole in different phenotypes followed the trend UMs < EMs < IMs < PMs, whereas dehydroaripiprazole serum level followed the trend UMs < EMs > IMs > PMs. What is new and conclusion Aripiprazole serum concentration differed significantly between EMs and IMs, but not between PMs. Whether this has clinical significance requires further evaluation by randomized trials.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Association between aripiprazole pharmacokinetics and CYP2D6 phenotypes: A systematic review and meta-analysis

et al. 2018

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“…В тоже время некоторые работы опровергают на-личие данной связи [9]. Замена гуанина на аденин в 1846 нуклеотидной паре гена CYP2D6 (CYP2D6*4, CYP2D6 1846G>T, rs3892097) приводит к наруше-нию сплайсинга и снижению активности изофер-мента CYP2D6, что должно приводить к замедлению скорости элиминации субстратов данного изофер-мента из организма [10].…”

Section: актуальностьunclassified

The Investigation of Influence of Genetic Profile on the Efficacy and Safety of Haloperidol in Patients With Alcohol Dependence

Zastrozhin¹,

Grishina²,

Сычев³

et al. 2016

Arhivʺ vnutr. med.

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“…Галоперидол подвергается N-деалкилиро-ванию при участии CYP3A4, преобразу-ясь в 4-хлорофенил-4-гидроксипиперидин и p-фторбензоилпропионовую кислоту. Связь активности CYP3A4 со скоростью биотрансформации галоперидола, была показана в ряде исследований на больных шизофренией [2,3,5]. В тоже время не-которые работы опровергают наличие данной связи [1].…”

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Association between the activity of enzyme CYP3A4 and profile of efficacy and safety of haloperidol in patiens with alcohol addiction

Застрожин¹,

Smirnov²,

Сычев³

et al. 2015

I.P. Pavlov Russian Medical Biological Herald

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Российская медицинская академия последипломного образования МЗРФ, г. Москва (1) Российский университет дружбы народов, г. Москва (2) Московский научно-практический центр наркологии Департамента здравоохранения города Москвы (3) Научно-исследовательский институт аллергологии и иммунологии, г. Москва (4) Галоперидол используется в наркологической практике для купирования ак-туализации влечения у больных, страдающих патологическим влечением к алко-голю, но эмпирический подбор его дозировки часто приводит к развитию у пациен-тов нежелательных лекарственных реакций. В биотрансформации галоперидола принимает участие изофермент микросомальной цепи цитохрома P-450 3A4, ак-тивность которого имеет высокую степень вариабельности. В исследовании при-няло участие 20 мужчин, страдающих алкоголизмом. Эффективность и безопас-ность терапии галоперидолом, определяли с помощью международных психомет-рических шкал. Активностью CYP3A4 определяли по содержанию в моче отноше-ния концентраций эндогенного субстрата данного изофермента и его метаболита (отношение 6-бетагидроксикортизол / кортизол). По результатам исследования бы-ли выявлены статистически значимые закономерности между активностью CYP3A4 и профилем эффективности и безопасности галоперидола.Ключевые слова: галоперидол, биотрансформация, CYP3A4, нежелательные ле-карственные реакции, патологическое влечение к алкоголю.

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The Influence of the CYP3A4*22 Polymorphism and CYP2D6 Polymorphisms on Serum Concentrations of Aripiprazole, Haloperidol, Pimozide, and Risperidone in Psychiatric Patients

Abstract: Heterozygous presence of CYP3A4*22 does not increase serum levels of antipsychotics metabolized by both CYP3A4 and CYP2D6, whereas CYP2D6 polymorphisms do affect serum levels to a limited extent.

Cited by 54 publications

References 59 publications

Association between aripiprazole pharmacokinetics and CYP2D6 phenotypes: A systematic review and meta-analysis

Association between aripiprazole pharmacokinetics and CYP2D6 phenotypes: A systematic review and meta-analysis

The Investigation of Influence of Genetic Profile on the Efficacy and Safety of Haloperidol in Patients With Alcohol Dependence

Association between the activity of enzyme CYP3A4 and profile of efficacy and safety of haloperidol in patiens with alcohol addiction

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