Impact of <i>CYP1A2</i> genetic polymorphisms on pharmacokinetics of antipsychotic drugs: a systematic review and meta‐analysis

Takuathung, Mingkwan Na; Hanprasertpong, Nutthiya; Teekachunhatean, Supanimit; Koonrungsesomboon, Nut

doi:10.1111/acps.12947

Cited by 26 publications

(20 citation statements)

References 62 publications

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“…CYP1A2*1F and CYP1A2*1C are important mutation types in East Asian populations. CYP1A2*1F mutation will increase the metabolic activity of CYP1A2 enzyme, while CYP1A2*1C will decrease the metabolic activity of CYP1A2 [32]. The occurrence frequency of CYP1A2*1F mutation can reach up to 40% or above, therefore it is not surprising that so many cohorts in this study were CYP1A2 ultra-rapid metabolizers.…”

Section: Discussionmentioning

confidence: 75%

An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics

Zhang¹,

Gu²,

Huang³

et al. 2021

Psychiatry and Clinical Psychopharmacology

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Background: Schizophrenia is a serious mental illness affecting 0.3% -0.7% of people in the whole world.It is a classic quantitative genetic disease and is affected by a variety of common and rare genetic variants.Methods: To facilitate personalized and precise medicine for schizophrenia treatment, we designed a program by genotyping a panel of related genes, including cytochrome P450 genes CYP1A2, CYP2D6, CYP3A4, dopamine 2 receptor gene (DRD2), 5-Hydroxytryptamine Receptor 1A and 2C genes (HTR1A and HTR2C) as well as melanocortin4 receptor (MC4R) gene, for the schizophrenia patients using MassArray time-of-ight mass spectrometry.Results: The program is tested in an observational clinical study conducted at the Hulunbuir Mental Health Center of China. In the study, a total of 254 patients diagnosed with schizophrenia were recruited and genotyped. The genotyping results were used to generate reports listing where the 16 included antipsychotics should be placed: 'Use as directed', 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' columns. However, the medication would not change regardless. 72 of the patients completed the 24-week follow-up observation, during which their PANSS scores were assessed at eight time points. For all of them, the PANSS scores dropped signi cantly, showing the effectiveness of the treatments. The treatments for those cohorts initially in the 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' categories were more effective than those in the 'Use as directed' category in a shorter term sense, up to three months. However, in the longer term, it was still those who were initially in the 'Use as directed' column fared better, whose PANSS scores dropped more signi cantly.Conclusions: This research indicated that our pharmacogenomic-based program could be a suitable and effective tool to facilitate precise medicine in schizophrenia treatment.

show abstract

Section: Discussionmentioning

confidence: 75%

An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics

Zhang¹,

Gu²,

Huang³

et al. 2021

Psychiatry and Clinical Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…and CYP1A2*1C are important mutation types in East Asian populations. CYP1A2*1F mutation will increase the metabolic activity of CYP1A2 enzyme, while CYP1A2*1C will decrease the metabolic activity of CYP1A2 [32]. The occurrence frequency of CYP1A2*1F mutation can reach up to 40% or above, therefore it is not surprising that so many cohorts in this study were CYP1A2 ultra-rapid metabolizers.…”

Section: Discussionmentioning

confidence: 75%

An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics

Shi¹,

Zhang

Gu³

et al. 2020

Preprint

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Background: Schizophrenia is a serious mental illness affecting 0.3% - 0.7% of people in the whole world. It is a classic quantitative genetic disease and is affected by a variety of common and rare genetic variants. Methods: To facilitate personalized and precise medicine for schizophrenia treatment, we designed a program by genotyping a panel of related genes, including cytochrome P450 genes CYP1A2, CYP2D6, CYP3A4, dopamine 2 receptor gene (DRD2), 5-Hydroxytryptamine Receptor 1A and 2C genes (HTR1A and HTR2C) as well as melanocortin4 receptor (MC4R) gene, for the schizophrenia patients using MassArray time-of-flight mass spectrometry. Results: The program is tested in an observational clinical study conducted at the Hulunbuir Mental Health Center of China. In the study, a total of 254 patients diagnosed with schizophrenia were recruited and genotyped. The genotyping results were used to generate reports listing where the 16 included antipsychotics should be placed: 'Use as directed', 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' columns. However, the medication would not change regardless. 72 of the patients completed the 24-week follow-up observation, during which their PANSS scores were assessed at eight time points. For all of them, the PANSS scores dropped significantly, showing the effectiveness of the treatments. The treatments for those cohorts initially in the 'Use with caution' or 'Use with caution and with frequent blood concentration monitoring' categories were more effective than those in the 'Use as directed' category in a shorter term sense, up to three months. However, in the longer term, it was still those who were initially in the 'Use as directed' column fared better, whose PANSS scores dropped more significantly. Conclusions: This research indicated that our pharmacogenomic-based program could be a suitable and effective tool to facilitate precise medicine in schizophrenia treatment.

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“…However, whether these in vitro findings translate in relevant in vivo significance remains unknown. In contrast, the general impact of CYP1A2 gene polymorphisms on the pharmacokinetics of CYP1A2dependent metabolized drugs were found to be low with no clinical implications (18). Among transient influences, several studies show that cigarette smoking leads to a short-lived but strong induction of CYP1A2 (3,34).…”

Section: Discussionmentioning

confidence: 99%

Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis

Wuensch

Heucke

Wizenty

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

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Dynamic liver function assessment by the [13C]methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic cytochrome P-450 (CYP) 1A2 activity. One proven strategy for preoperative risk assessment in liver surgery includes the combined assessment of the dynamic liver function by the LiMAx test, the volumetric analysis of the liver, and calculation of future liver remnant function. This so-called volume-function analysis assumes that the remaining CYP1A2 activity in any tumor lesion is zero. The here presented study aims to assess the remaining CYP1A2 activities in different hepatic tumor lesions and its consequences for the preoperative volume-function analysis in patients undergoing liver surgery. The CYP1A2 activity analysis of neoplastic lesions and adjacent nontumor liver tissue from resected tumor specimens revealed a significantly higher CYP1A2 activity (median, interquartile range) in nontumor tissues (35.5, 15.9–54.4 µU/mg) compared with hepatocellular adenomas (7.35, 1.2–32.5 µU/mg), hepatocellular carcinomas (0.18, 0.0–2.0 µU/mg), or colorectal liver metastasis (0.17, 0.0–2.1 µU/mg). In nontumor liver tissue, a gradual decline in CYP1A2 activity with exacerbating fibrosis was observed. The CYP1A2 activity differences were also reflected in CYP1A2 protein signals in the assessed hepatic tissues. Volume-function analysis showed a minimal deviation compared with the current standard calculation for hepatocellular carcinomas or colorectal liver metastasis (<1% difference), whereas a difference of 11.9% was observed for hepatocellular adenomas. These findings are important for a refined preoperative volume-function analysis and improved surgical risk assessment in hepatocellular adenoma cases with low LiMAx values. NEW & NOTEWORTHY The cytochrome P-450 (CYP) 1A2-dependent maximal liver function capacity test reflects the overall functional capacity of the liver. To which extent hepatocellular tumors harbor CYP1A2 activity and thus contribute to the maximal liver function capacity test outcome is unknown. We here show that hepatocellular adenomas but not hepatocellular carcinomas or colorectal liver metastasis contain significant residual CYP1A2 activity. These findings are important for an improved preoperative volume-function analysis and an accurate surgical risk assessment in hepatocellular adenoma cases.

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Impact of CYP1A2 genetic polymorphisms on pharmacokinetics of antipsychotic drugs: a systematic review and meta‐analysis

Abstract: This study suggests that CYP1A2 genetic polymorphisms have no significant impact on the pharmacokinetics of CYP1A2-metabolized antipsychotic drugs. CYP1A2 genotyping may have no clinical implications for personalized dosing of CYP1A2-metabolized antipsychotic drugs.

Cited by 26 publications

References 62 publications

An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics

An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics

An Effective Method to Facilitate Personalized and Precise Medicine for Schizophrenia Treatment Based on Pharmacogenomics

Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis

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