Acta Pharm Sin B. 2025 Mar;15(3):1571-1588. doi: 10.1016/j.apsb.2025.02.005. Epub 2025 Feb 11.

ABSTRACT

eIF3a is a N 6-methyladenosine (m6A) reader that regulates mRNA translation by recognizing m6A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m6A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m6A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

PMID:40370535 | PMC:PMC12069248 | DOI:10.1016/j.apsb.2025.02.005

Res Ethics. 2024 Apr;20(2):363-387. doi: 10.1177/17470161231207739. Epub 2023 Oct 31.

ABSTRACT

This study aimed to explore stakeholders' perspectives on the ethical considerations for returning individual pharmacogenomics research results to people living with HIV. A qualitative approach to investigation involved five focus group discussions with 30 Community representatives, 12 key informant interviews with researchers, and 12 in-depth interviews with research ethics committee members. In total, 54 stakeholders who were involved in pharmacogenomics research and HIV treatment and care contributed to the data collection between September 2021 and February 2022. The study explored five prominent themes: (i) defining the nature of research results to return to participants; (ii) preparing research participants to receive their results; (iii) obtaining informed consent for the return of results; (iv) opinions on health personnel to return the results to participants; and (v) opinions on how research results should be communicated to participants. Respondents identified various strategies for the return of individual results with minimal ethical risks including the setting up of a diverse and independent committee to undertake a risk-benefit assessment based on local context; ongoing discussions about the possible kinds of results and their implications throughout the study; and employing genetic counsellors to communicate results to participants. The strategies identified in this study should be further studied and independently verified.

PMID:40370487 | PMC:PMC12077594 | DOI:10.1177/17470161231207739

Breast Cancer Res. 2025 May 14;27(1):79. doi: 10.1186/s13058-025-02020-x.

ABSTRACT

Mutations in ESR1 play a critical role in resistance to endocrine therapy (ET) in hormone receptor-positive (HR +)/HER2- metastatic breast cancer (MBC). Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. While most studies have utilized liquid biopsy (LB) for mutation detection, the role of formalin-fixed paraffin-embedded (FFPE) tissue biopsy in this context remains unclear. In this study, we analyzed a cohort of HR + /HER2- MBC patients who experienced resistance to ET and CDK4/6 inhibitors. Next-generation sequencing (NGS) was performed on FFPE biopsy samples obtained from metastatic sites at the time of disease progression. ESR1 mutations were detected in 24 out of 38 patients (63.2%), with p.D538G identified in 10 patients (45.5%) and p.Y537S in 6 patients (27.2%) as the most frequent alterations. One patient exhibited dual ESR1 mutations, and a recurrent ESR1-CCDC170 gene fusion was identified, underscoring the diversity and potential interplay of genetic alterations driving resistance in HR + /HER2- MBC. Notably, lung metastases were significantly more common in ESR1 mutant cases (8/24, 33.3%) compared to wild-type cases (1/14, 7.1%), while liver metastases showed no difference between mutant (12/24, 50.0%) and wild-type groups (7/14, 50.0%). Co-mutations in actionable pathways, particularly PIK3CA, were observed in n = 10 ESR1 mutant tumors (41.6%), highlighting their contribution to resistance mechanisms and posing significant challenges for treatment selection, as these alterations may necessitate combination therapies to effectively target multiple resistance pathways. This study presents new insights into the prevalence and clinical significance of ESR1 mutations in HR + /HER2- MBC, highlighting the potential utility of FFPE biopsy samples as a viable alternative or complementary approach to LB for mutation detection, particularly in resource-limited settings where access to ctDNA analysis may be constrained.

PMID:40369610 | DOI:10.1186/s13058-025-02020-x

BMC Complement Med Ther. 2025 May 14;25(1):176. doi: 10.1186/s12906-025-04901-2.

NO ABSTRACT

PMID:40369508 | DOI:10.1186/s12906-025-04901-2

EMBO Mol Med. 2025 May 14. doi: 10.1038/s44321-025-00241-3. Online ahead of print.

ABSTRACT

Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in three clusters, including an IMiD degron in zinc finger cluster one (ZFC1). Surprisingly, IMiDs do not inhibit the growth of SALL4-expressing cancer cells. To overcome this limit, we focused on a non-IMiD domain, SALL4 zinc finger cluster four (ZFC4). By combining ZFC4-DNA crystal structure and an in silico docking algorithm, in conjunction with cell viability assays, we screened several chemical libraries against a potentially druggable binding pocket, leading to the discovery of SH6, a compound that selectively targets SALL4-expressing cancer cells. Mechanistic studies revealed that SH6 degrades SALL4 protein through the CUL4A/CRBN pathway, while deletion of ZFC4 abolished this activity. Moreover, SH6 treatment led to a significant 87% tumor growth inhibition of SALL4+ patient-derived xenografts and demonstrated good bioavailability in pharmacokinetic studies. In summary, these studies represent a new approach for IMiD independent drug discovery targeting C2H2 transcription factors such as SALL4 in cancer.

PMID:40369156 | DOI:10.1038/s44321-025-00241-3

Nature. 2025 May 14. doi: 10.1038/s41586-025-08994-0. Online ahead of print.

ABSTRACT

The anti-tumour effect of radiotherapy beyond the treatment field-the abscopal effect-has garnered much interest1. However, the potentially deleterious effect of radiation in promoting metastasis is less well studied. Here we show that radiotherapy induces the expression of the EGFR ligand amphiregulin in tumour cells, which reprogrammes EGFR-expressing myeloid cells toward an immunosuppressive phenotype and reduces phagocytosis. This stimulates distant metastasis growth in human patients and in pre-clinical mouse tumour models. The inhibition of these tumour-promoting factors induced by radiotherapy may represent a novel therapeutic strategy to improve patient outcomes.

PMID:40369065 | DOI:10.1038/s41586-025-08994-0

Microb Pathog. 2025 May 12:107701. doi: 10.1016/j.micpath.2025.107701. Online ahead of print.

ABSTRACT

5-Fluorouracil (5-FU) is a chemotherapeutic agent that disrupts pyrimidine metabolism, which can interact with gut microbiota, potentially causing dysbiosis and promoting antibiotic resistance. This study analyzed its antimicrobial and antibiofilm effects on Escherichia coli and Enterococcus spp. The Minimum Inhibitory Concentrations (MIC) and Minimum Biofilm Eradication Concentrations (MBEC) of 5-FU were determined against 17 clinical isolates, including resistant and susceptible strains. Biofilm formation and viability were assessed using crystal violet staining and resazurin assays, respectively. Growth curves were generated by exposing selected strains to increasing concentrations of 5-FU and monitoring Optical Density (OD) at 630 nm over 24 hours. Flow cytometry was used to evaluate membrane integrity, using Propidium Iodide (PI), and Reactive Oxygen Species (ROS) production, with DCFH-DA, while Scanning Electron Microscopy (SEM) was used to show the structural alterations in bacterial cells. 5-FU MIC values ranged from 128-512 μM against E. coli and 1-32 μM against Enterococcus spp., with higher MICs observed against resistant strains. MBEC values exceeded planktonic MICs by up to 16-fold for E. coli and 64-fold for Enterococcus spp., ranging from 128 to >2048 μM. At MIC concentrations, membrane damage was increased in both species, while at subinhibitory concentrations, ROS production was exclusively detected in Enterococcus faecalis strains. SEM revealed severe structural alterations, including pore formation, cell shrinkage, cytoplasmic leakage, and cell disintegration highlighting the impact of 5-FU on bacterial morphology. These findings highlight the antibacterial effect of 5-FU, underscoring its potential impact on gut microbial dynamics and the selective pressures it exerts during chemotherapy.

PMID:40368067 | DOI:10.1016/j.micpath.2025.107701

Cancer Treat Rev. 2025 May 10;137:102956. doi: 10.1016/j.ctrv.2025.102956. Online ahead of print.

ABSTRACT

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have reshaped the treatment paradigm of hormone receptor positive (HR + )/HER2-negative breast cancer in both adjuvant and metastatic settings. However, their metabolism via the cytochrome P450 (CYP3A4) pathway poses a high risk of clinically relevant drug-drug interactions (DDIs), requiring vigilant therapeutic strategies. This review provides a comprehensive analysis of the pharmacokinetics, metabolism, and interaction profiles of palbociclib, ribociclib, and abemaciclib, emphasizing their differential DDI risks. Among these agents, ribociclib has been associated with a higher risk of QTc prolongation and CYP3A4-mediated interactions in some studies, whereas abemaciclib demonstrates a relatively favorable DDI profile. However, data remain limited and are largely derived from indirect comparisons or pharmacovigilance analyses. We further examine the clinical implications of drug-drug interactions with frequently co-prescribed agents, including proton pump inhibitors, antifungal medications, anticoagulants, and lipid-lowering therapies. Practical recommendations regarding drug selection, therapeutic drug monitoring, and dose adjustment are discussed with attention to the individual characteristics of each CDK4/6i. Dose modifications and monitoring in patients with renal or hepatic impairment are also discussed. Emerging pharmacogenomic data suggest that genetic polymorphisms in CYP3A4 and ABCG2 influence drug exposure and toxicity, reinforcing the need for personalized treatment approaches. As the use of CDK4/6i expands across different breast cancer settings, addressing DDIs through precision medicine strategies such as pharmacogenomic profiling, physiologically based pharmacokinetic modeling, and artificial intelligence-guided clinical support will be essential to personalize therapy and optimize safety.

PMID:40367730 | DOI:10.1016/j.ctrv.2025.102956

Pharmacogenomics. 2025 May 14:1-6. doi: 10.1080/14622416.2025.2504864. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore the impact of low miR-369-3p expression on the resistance of PC-9 cells to osimertinib.

METHODS: The PC-9/AZD9291 cell line was established with osimertinib. Real-time quantitative PCR was employed to measure the expression levels of miR-369-3p in both PC-9 and PC-9/AZD9291 cells, and Western blotting was utilized to detect PTPN12 protein expression. A dual-luciferase reporter assay was conducted to investigate the target relationship between miR-369-3p and PTPN12. CCK8 assays were performed to evaluate the impact of miR-369-3p inhibition on drug resistance.

RESULTS: In comparison to PC-9 cells, there was a significant upregulation of miR-369-3p and downregulation of PTPN12 protein in PC-9/AZD9291 cells (p < 0.05). Transfection with the miR-369-3p inhibitor resulted in decreased levels of miR-369-3p and increased expression of PTPN12 protein in PC-9/AZD9291 cells (p < 0.05). Conversely, transfection with miR-369 mimics led to an increase in miR-369-3p levels accompanied by a decrease in PTPN12 protein (p < 0.05). Notably, treatment with the miR-369-3p inhibitor lowered the IC50 value for PC-9/AZD9291 cells; however, following downregulation of PTPN12 using PTPN12-siRNA, sensitivity due to low expression of miR-369-3p was significantly diminished (p < 0.05).

CONCLUSION: miR-369-3p plays a crucial role in modulating drug resistance in PC-9/AZD9291 cells against osimertinib through regulation of PTPN12.

PMID:40366733 | DOI:10.1080/14622416.2025.2504864

Int J Mol Sci. 2025 May 3;26(9):4356. doi: 10.3390/ijms26094356.

ABSTRACT

Recently, an old drug, disulfiram, has been shown to reduce cocaine intake by inhibiting dopamine beta (β)-hydroxylase. Its effectiveness was also reported in opioid treatment, as disulfiram attenuated morphine-induced tolerance and dependence. A similar mechanism of action was evident in a selective inhibitor of DβH, nepicastat, particularly in the aspect of cocaine-seeking behavior. Hence, the objective of this study was to verify whether or not nepicastat reproduces disulfiram activity in pain reduction. Moreover, determination of its likely biological effects resulting from interactions with targets other than DβH has been given, in particular acetylcholinesterase. As was found, nepicastat was characterized by the absence of desired antinociceptive activity, though its co-administration with morphine resulted in a dose- and time-dependent enhancement of morphine-induced analgesic effect and attenuation of tolerance. Similarly, nepicastat was found to manifest antimicrobial potency against selected bacterial strains, although the effect was found to be weak. Intriguingly, this compound interacted with acetylcholinesterase through inhibition of its activity. These results clearly indicate nepicastat as a potent molecule that exhibits various biological effects. This, in turn, suggests its possible application in pathological conditions that still require effective treatment.

PMID:40362592 | DOI:10.3390/ijms26094356

Int J Mol Sci. 2025 May 1;26(9):4285. doi: 10.3390/ijms26094285.

ABSTRACT

In this review, we explore the biomarkers of different psychiatric disorders, such as major depressive disorder, generalized anxiety disorder, schizophrenia, and bipolar disorder. Moreover, we show the interplay between genetic and environmental factors. Novel techniques such as genome-wide association studies (GWASs) have identified numerous risk loci and single-nucleotide polymorphisms (SNPs) implicated in these conditions, contributing to a better understanding of their mechanisms. Moreover, the impact of genetic variations on drug metabolisms, particularly through cytochrome P450 (CYP450) enzymes, highlights the importance of pharmacogenomics in optimizing psychiatric treatment. This review also explores the role of neurotransmitter regulation, immune system interactions, and metabolic pathways in psychiatric disorders. As the technology advances, integrating genetic markers into clinical practice will be crucial in advancing precision psychiatry, improving diagnostic accuracy and therapeutic interventions for individual patients.

PMID:40362522 | DOI:10.3390/ijms26094285

Int J Mol Sci. 2025 Apr 29;26(9):4245. doi: 10.3390/ijms26094245.

ABSTRACT

The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29-0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09-0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23-0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14-0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02-0.70; p = 0.02, and OR 0.08, 95% CI 0.01-0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC.

PMID:40362483 | DOI:10.3390/ijms26094245

Int J Mol Sci. 2025 Apr 25;26(9):4106. doi: 10.3390/ijms26094106.

ABSTRACT

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The precursor of CRC is a colorectal polyp, of which adenoma is the most common histological type. The initial step in CRC development is the gradual accumulation of a series of genetic and epigenetic alterations in the normal colonic epithelium. Genetic alterations play a major role in a subset of CRCs, but the pathophysiological contribution of epigenetic aberrations has recently attracted attention. Epigenetic marks occur early in cancer pathogenesis and are therefore important molecular hallmarks of cancer. This makes some epigenetic alterations clinically relevant for early detection not only of CRC but also of precancerous polyps. In this review we focus on three types of non-coding RNAs as epigenetic regulators: miRNA, lncRNA, and lncRNAs, highlighting their biomarker potential.

PMID:40362348 | DOI:10.3390/ijms26094106

Nat Genet. 2025 May 13. doi: 10.1038/s41588-025-02189-z. Online ahead of print.

ABSTRACT

Obsessive-compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D1 and D2 type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index.

PMID:40360802 | DOI:10.1038/s41588-025-02189-z

Nat Metab. 2025 May 13. doi: 10.1038/s42255-025-01308-8. Online ahead of print.

NO ABSTRACT

PMID:40360757 | DOI:10.1038/s42255-025-01308-8

Ann Hum Genet. 2025 May 13:e12601. doi: 10.1111/ahg.12601. Online ahead of print.

ABSTRACT

Pharmacogenomics, the use of germline genomic data to guide prescription to improve effective and safer medication, holds promise as a clinical intervention. To date in most health systems, there has been limited uptake of pharmacogenomic testing confined to a few single drug-gene associations. Here, we describe the current reactive model of single gene testing and the potential for this to change to a pre-emptive panel or genome-based approach. For this change to occur, three major challenges need to be addressed-the pharmacogenomic testing approach, the digital and data integration, and service delivery models. We explore some of the potential solutions and how pharmacogenomics can be integrated into routine care at scale for patient benefit.

PMID:40358420 | DOI:10.1111/ahg.12601

Cells. 2025 Apr 22;14(9):622. doi: 10.3390/cells14090622.

ABSTRACT

In the original publication [...].

PMID:40358202 | DOI:10.3390/cells14090622

Front Pharmacol. 2025 Apr 28;16:1539870. doi: 10.3389/fphar.2025.1539870. eCollection 2025.

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as promising therapeutics for heart failure (HF). Nevertheless, evidence supporting the mechanism of SGLT2i efficacy in HF patients is currently limited. Genetic variation in SLC5A2 (encoding SGLT2) may influence HF progression and SGLT2i response, as well as inform potential SGLT2i mechanisms. Thus, this study investigated associations between SLC5A2 variation and clinical outcomes in SGLT2i-naïve and dapagliflozin-treated HF cohorts.

METHODS: We analyzed two HF cohorts to identify variants associated with SGLT2i response pathways. Adjusted Cox proportional-hazard regression models were used to assess the effect of SLC5A2 variation on a primary composite outcome of cardiovascular (CV) hospitalization or all-cause mortality in SGLT2i-naïve patients, and HF hospitalization or CV death in dapagliflozin-treated patients. The initial cohort comprised 327 American HF patients naïve to SGLT2i throughout the study. Subsequently, a prospective cohort study of 190 Egyptian SGLT2i-naïve HF patients treated with dapagliflozin was analyzed. In this cohort, SNPs in UGT2B4 and SLC2A1 were also investigated. Changes in NT-proBNP levels, KCCQ-12 scores, echocardiographic parameters, and eGFR throughout 6-month follow-up were tested with linear regression models as secondary outcomes.

RESULTS: In SGLT2i-naïve patients, rs3813008 (SLC5A2) was significantly associated with reduced risk of the composite outcome of all-cause death or hospitalization (HR = 0.65, 95% CI: 0.47-0.89, P = 0.008). In the dapagliflozin-treated cohort, rs3813008 was also associated with death or hospitalization, but with increased risk in treated patients (HR = 3.38, 95% CI: 1.35-8.42, P = 0.008).

CONCLUSION: Our study suggests that SLC5A2 variation is associated with clinical outcomes in SGLT2i-naïve and treated HF patients, warranting further investigation of SLC5A2 and SGLT2i interactions.

PMID:40356983 | PMC:PMC12066643 | DOI:10.3389/fphar.2025.1539870

Future Oncol. 2025 May 13:1-14. doi: 10.1080/14796694.2025.2501517. Online ahead of print.

ABSTRACT

AIMS: This study identifies single-nucleotide polymorphisms (SNPs) associated with cellular response to cyclophosphamide (CTX) using phosphoramide mustard (PM), its primary cytotoxic metabolite, and explores the downstream consequences for breast cancer (BC) patients.

METHODS: We analyzed 1,978,545 SNPs from EBV-transformed lymphoblastic cell lines (LCLs) derived from 53 unrelated European individuals, in a genome-wide association study using cellular PM sensitivity data. We filtered SNPs associated with PM sensitivity (p < 5 × 10-5) predicted to overlap with regulatory elements in breast tissue using a chromatin state prediction model. We then assessed the consequences using LCL transcriptomic data and data from BC patients treated with (ACT-BC; N = 155) and without CTX.

RESULTS: Twenty SNPs were filtered out including rs12408401, which was associated with PM resistance (p = 3.89 × 10-5), potentially disrupted a CTCF-loop, and was associated with increased RFX5 expression (p = 0.036), which was associated with poor disease-free interval in ACT-BC patients (HR = 5.32; p = 0.028); and rs784562, which was associated with improved PM sensitivity (p = 6.41 × 10-6), potentially altered nearby enhancer functionality, and reduced expression of KRT72 which was associated with poor progression-free survival in ACT-BC patients (HR = 3.61; p = 0.040).

CONCLUSION: Our study identifies SNPs significantly associated with cellular CTX response with potential mechanistic and clinical relevance, thereby providing insights toward optimized CTX treatment strategies.

PMID:40356407 | DOI:10.1080/14796694.2025.2501517

J Psychopharmacol. 2025 May 12:2698811251337387. doi: 10.1177/02698811251337387. Online ahead of print.

ABSTRACT

INTRODUCTION: Psychopharmacotherapy with mirtazapine is commonplace. Lower serum concentrations of mirtazapine were reported in smokers due to CYP1A2 induction. However, no previous study that investigated CYP1A2 genetics and mirtazapine treatment considered CYP1A2-inducing parameters.

AIM: We aimed to investigate the association of CYP1A2 variants, mirtazapine serum concentration, and treatment outcome, considering the smoking status of the patients.

METHODS: Two depression cohorts were investigated for the association between serum concentration and treatment response of mirtazapine and CYP1A2-163C>A (rs762551) and -3860G>A (rs2069514) genotype groups, also considering smoking status, sex, and age of the patients. In total, 124 patients (82 non-smokers and 42 smokers) were eligible for the analyses.

RESULTS: Dose-corrected serum concentration (CD) of mirtazapine was associated with smoking status, sex, and age, with lower CD in smokers, females, and older patients. Considering non-smokers and genotype-grouped smokers, CD of mirtazapine in CYP1A2 normal metabolizer smokers (N = 6) did not differ from CD of non-smokers. By contrast, smokers carrying the CYP1A2*1A/*1F and *1F/*1F genotype groups showed 34.4% and 33.4% lower mirtazapine CD compared to non-smokers.

DISCUSSION: As yet, for clinical practice, it may be more relevant to focus on smoking status than on the CYP1A2 gene variants. Considering the relevant impact of smoking on the mirtazapine CD, physicians should monitor an increase in side effects due to the expected increase in mirtazapine serum concentrations. In these cases, measurement of mirtazapine CD and/or subsequent dosage reduction is recommended. The clinical relevance of CYP1A2 genotyping prior to treatment with drugs metabolized by CYP1A2 needs further investigation.

PMID:40353511 | DOI:10.1177/02698811251337387