Construction of multi-component covalent organic framework coated stainless steel fiber for efficient microextraction of psychiatric drugs: experiments and clinical applications.

Prostate cancer is driven by androgen receptor activation caused by (dihydro)testosterone. Abiraterone, which is used against metastatic castration-resistant prostate cancer (mCRPC), improves survival by irreversibly inhibiting CYP17 to reduce androgen and cortisol synthesis. As such, cortisol is a potential biomarker for androgen suppression. This study assessed the impact of pharmacokinetically (PK)-guided interventions after therapeutic drug monitoring (TDM) of abiraterone on cortisol plasma concentrations as a biomarker for CYP17 inhibition in patients with mCRPC. In this retrospective cohort study, patients with mCRPC receiving abiraterone with TDM based on abiraterone plasma concentrations were compared with a historical cohort receiving standard care. The primary end point was adequate CYP17 inhibition, defined as cortisol plasma concentration <6.18 nmol/L. Secondary end points included the time course of cortisol plasma concentrations and the impact of PK-guided interventions. A total of 103 patients were included in the TDM population, and 99 were included in the historical cohort. Median cortisol plasma concentrations were lower in the TDM population [1.9 (95% confidence interval 1.1-5.8) versus 3.9 (95% confidence interval 1.4-12.4] nmol/L, P = 0.01), with more patients achieving adequate CYP17 inhibition (75.7% versus 62.6%, P = 0.06). Of the 32 patients with evaluable data before and after PK-guided intervention, 96.9% reached adequate abiraterone concentrations; however, no significant improvement in adequate CYP17 inhibition was observed when comparing cortisol before and after PK-guided intervention (81.3% versus 71.9%, P = 0.45). In the TDM population, lower cortisol plasma concentrations were observed. However, it is unclear whether increasing abiraterone exposure through PK-guided interventions decreased cortisol plasma concentrations.

We aimed to build a serum proteomics-based model to predict primary nonresponse (PNR) to infliximab (IFX) in pediatric colonic inflammatory bowel disease, with early proactive therapeutic drug monitoring. Children in the prospective Canadian Children IBD Network with ulcerative colitis (UC), inflammatory bowel disease unclassified (IBD-U), or colonic Crohn's disease (CD) with serum pre-IFX were eligible. We defined PNR as IFX cessation plus surgery/drug switch within 6 months. We compared clinical features between groups (Mann Whitney U, chi-square test). We measured serum proteins with Olink Inflammation/Immune Response panels. We built a regularized regression (generalized linear model [GLM]) machine learning model and compared its performance with other models with 10-fold cross-validation repeated 10 times (receiver-operating characteristic/precision-recall curves, predictive score separation). We ranked proteomic features by SHAP (SHapley Additive exPlanations) analysis. We hypothesized that treatment-naïve serum would be more informative than treatment-exposed serum. We included 96 patients: 71 UC/IBD-U (23 nonresponders), 42 treatment-naïve (12 nonresponders); and 25 CD, 19 treatment-naïve. Pre-third and pre-fourth dose serum infliximab levels were similar and robust (>10 µg/mL) in primary nonresponders and responders. Predictive performance was superior for diagnostic, treatment-naïve samples; the GLM showed good ability to separate primary nonresponders and responders. The GLM model on treatment-naïve serum (area under the curve ∼0.75) had better specificity to predict responders and included 21 proteins, with CSF1 and ITM2A top ranked. UC/IBD-U responders more often were steroid refractory and received infliximab as first maintenance. A serum proteomics linear model on treatment-naïve serum best predicted PNR. Findings require external validation but suggest that the diagnostic/pretreatment window may be key to understanding biology central to effective drug sequencing.

In France, therapeutic patient education is a cornerstone of posttransplant care. However, substantial variability persists in how immunosuppressive therapies are addressed across transplant centers, potentially affecting adherence and patient outcomes. To reduce this heterogeneity, the French-Speaking Society for Transplantation (Société Francophone de Transplantation) launched a national initiative to harmonize educational practices on immunosuppressive therapy. Following a national survey that highlighted inconsistent and sometimes conflicting messages delivered to patients, a multidisciplinary working group comprising transplant physicians, pharmacists, pharmacologists, nurses, and representatives of patient associations developed a practical reference guide. This guide aims to help healthcare teams deliver coherent, evidence-based messages on key aspects of immunosuppressant management. Adaptable to local workflows and patient needs, it covers 7 core domains: timing of administration; relation to meals; missed-dose management; food and drug interactions; travel across time zones; handling of dosage forms; and special situations such as vomiting or swallowing disorders. It also underscores the critical role of therapeutic drug monitoring in supporting individualized care and strengthening adherence. This nationally coordinated initiative illustrates how collaborative, cross-disciplinary efforts can enhance the quality and consistency of patient education in transplantation. Its structured approach may serve as a model for other countries seeking to optimize adherence and long-term outcomes through standardized educational practices.

Guanfacine, an enteral α2-adrenergic and imidazoline receptor agonist, has occasionally been described in critical care as an adjunctive agent for the management of delirium and suspected dexmedetomidine withdrawal. However, its pharmacokinetic behavior during venovenous extracorporeal membrane oxygenation (VV ECMO) combined with continuous venovenous hemofiltration (CVVH) has not been defined. A 64-year-old man with severe COVID-19 pneumonia developed refractory hypoxemia, requiring VV ECMO and CVVH for multiorgan support. Enteral guanfacine 7 mg/d was initiated on day 14 to transition from dexmedetomidine sedation. Steady-state trough plasma and ultrafiltrate guanfacine concentrations of 3.2 and 0.5 ng/mL, respectively, were obtained on day 24, yielding a sieving coefficient of 0.16 and convective clearance of 0.267 mL/min. ECMO adsorption was negligible based on expected pharmacokinetic concentrations. The patient was decannulated from ECMO on day 30, and guanfacine was successfully tapered over 7 days without withdrawal symptoms occurring. In this patient, high-dose guanfacine achieved predicted plasma concentrations during concurrent VV ECMO and CVVH, with minimal extracorporeal clearance or circuit sequestration. These findings suggest that standard dosing is appropriate in similar patients and support the use of guanfacine as a viable transition agent during dexmedetomidine weaning. Prospective pharmacokinetic studies in ECMO-supported patients are warranted.

Applications of mass spectrometry in the routine diagnostic medical laboratory - a status report 2025.

Despite important advancements in diagnostic modalities, routine use of therapeutic drug monitoring (TDM) and newer antifungal therapies, there is a paucity of contemporary data regarding clinical characteristics and outcomes of invasive aspergillosis (IA) in the United States. Single-center, retrospective cohort study of hospitalized patients between 2015 and 2020, who had active hematological malignancy (HM) or had undergone transplantation and cellular therapy (TCT) and had probableorproven IA. Sixty-two patients with probableorproven IA, including 21 HM and 41 TCT, were identified. Forty-four percent of the cases corresponded to breakthrough IA. Bronchoalveolar lavage galactomannan was ≥ 1 in 71% and ≥ 0.5 in 88%, while serum galactomannan was ≥ 0.5 in only 34%. Among assessable patients (n = 59), 90-day partial or complete response to antifungal therapy occurred in 39%. All-cause mortality for the entire cohort was 22% at 30days and 46% at 90days. IA attributable mortality was 18% at 30days and 38% at 90days. Achieving therapeutic antifungal serum levels was associated with a reduction in all-cause mortality, while prior clinically significant CMV infection (aOR 9.65, 95% CI 1.34-69.6; P = 0.025) and relapsed/refractory hematological disease (aOR 8.5, 95% CI 2.23, 32.4; P = 0.002) were associated with higher IA attributable mortality. Despite advancements in diagnosis and treatment, IA remains associated with poor outcomes in hematological patients in the contemporary era. Newer antifungals and improved strategies for monitoring and prevention of IA in these vulnerable patient populations are urgently needed.

This study investigated the effects of temperature and concentration on the short-term stability of colistin and colistin methanesulphonate in three biological matrices; whole blood, plasma and serum. Human whole blood, plasma or serum containing colistin (2; 10; 20 mg/L) or colistin methanesulphonate (2; 10; 20 mg/L) was stored at room temperatrure or at 37 °C for a predetermined time interval. The concentrations of colistin in colistin spiked samples, and formed colistin in colistin methanesulphonate spiked samples, were analysed by LC-MS method. Findings indicate that colistin A and B were stable at the room temperature, but degradation accelerated at 37 °C, particularly at lower concentrations. The conversion of CMS to colistin was also temperature-dependent, where the concersion was significantly accelerated at elevated temperatures. Freeze-thaw stability were tested, COL A as well as COL B were stable for at least three freeze-thaw cycles. These results underscore the importance of rapid sample processing to ensure reliable therapeutic drug monitoring and emphasize the importance of considering temperature and concentration factors in clinical practice to optimise dosing and minimise toxicity. Further research is required to investigate the full range of factors affecting the stability of colistin and colistin methanesulphonate in biological matrices.

Background Critically ill patients exhibit acute physiological changes leading to marked antibiotic exposure variability and an increased probability of either subtherapeutic or potentially toxic exposures. Beta-lactam antibiotics are often affected by these physiological changes, leading to variable and often subtherapeutic exposures. Furthermore, although this medication class is associated with minimal concentration-related adverse effects, recent evidence suggests that beta-lactams may be associated with neurotoxicity and nephrotoxicity. Therefore, methods to increase the probability of a therapeutic exposure may be beneficial for critically ill patients. Model Informed Precision Dosing (MIPD) is an emerging strategy using advanced computer models to individualise dosing in this vulnerable population with or without therapeutic drug monitoring (TDM). By tailoring therapy to the individual patient scenario, MIPD aims to improve clinical outcomes by enhancing the likelihood of effective and safe therapy. Summary MIPD-guided beta-lactam antibiotic dosing may improve the probability of attaining target therapeutic exposures and clinical cure rates compared to standard fixed dosing in critically ill patients. Moreover, MIPD allows clinicians to target higher beta-lactam antibiotic exposures whilst minimising the risk of toxicity, when the goal of treatment is both improving clinical cure rates and suppressing the probability of antibiotic resistance emergence. No differences in mortality and adverse event reduction compared to standard dosing has been currently identified in the literature. However, the exact potential of MIPD has yet to be determined given the significant limitations in the current evidence base, including heterogeneous study designs, small sample sizes, inconsistent implementation strategies and variable outcome definitions. Clinical practice and future research should optimise MIPD performance by selecting appropriate and innovative beta-lactam antibiotic exposure models, as well as identify methods to instigate early MIPD dosing and timely TDM dose adjustments. This may further improve clinical and economic outcomes for critically ill patients.

Dalbavancin is a promising option for the treatment of complex gram-positive infections. However, the optimal dosing regimen to ensure adequate drug exposure during prolonged treatment courses remains debate. To evaluate whether an intravenous dalbavancin regimen of 1500 mg administered on days 1, 15 and 43 achieves validated serum concentration targets for infections requiring 12 weeks of treatment. We conducted a retrospective bicentric study including patients who received three 1500 mg doses of dalbavancin intended to provide 12 weeks of treatment coverage between January 2020 and May 2024. Patients' characteristics, microbiological data, and dalbavancin concentrations measured before reinjection on days 15, 43 and 90 were collected. We targeted a total dalbavancin plasma concentration of ≥8.04 mg/L, validated for Staphylococcus spp. strains with a MIC ≤0.125 mg/L. Concentrations were compared according to body mass index (≥30 kg/m2) and albumin level (≥30 g/L). Forty-two patients (39 bone and joint infections and three vascular infections) were included. Dalbavancin serum trough concentrations exceeded 8.04 mg/L for all available measurements (76/76) across the different monitored time points during the 12-week treatment period. Although lower concentrations were observed in patients with hypoalbuminemia or obesity, all measured values remained above the target threshold. These results suggest that a three-dose dalbavancin regimen administered on days 1, 15, and 43 may achieve validated pharmacokinetic targets and maintain therapeutic exposure over a 12-week period for staphylococcal infections with a dalbavancin MIC ≤0.125 mg/L. Therapeutic drug monitoring should be performed for patients with hypoalbuminemia or obesity until larger studies confirm these findings, and for strains with an MIC >0.125 mg/L.

The aim of this study was to investigate the fluctuations in isavuconazole concentrations and to identify influencing factors in Chinese patients with haematological malignancies. A retrospective analysis was conducted on patients with haematological malignancies who received their first standard dose of isavuconazole treatment in 2024. Statistical analysis of trough concentrations of isavuconazole, demographics and clinical characteristics over 60 days of treatment was performed. A nomogram was constructed based on independent risk factors to predict isavuconazole trough concentrations > 7 mg/L. A total of 63 patients with a median age of 54 (39-63) years and 390 isavuconazole plasma concentrations with a median value of 5.68 mg/L (range 1.24-16.49 mg/L) were included. The median intra- and inter-individual coefficients of variation were 15.0% and 43.3%, respectively. In univariate and multivariate analysis, isavuconazole levels > 7 mg/L on day 7 were significantly associated with body mass index (BMI) and albumin (ALB). Compared to patients with a BMI > 21.0 kg/m2, those with a BMI ≤ 21.0 kg/m2 exhibited a 15.88-fold increased risk of isavuconazole trough concentrations > 7 mg/L. Similarly, patients with ALB ≥ 36.4 g/L showed a 4.71-fold higher risk of elevated isavuconazole levels than those with ALB < 36.4 g/L. A nomogram model for effectively predicting the risk of isavuconazole concentrations exceeding 7 mg/L based on BMI and ALB results was successfully established. Patients with haematological malignancies treated with isavuconazole show modest plasma concentration variability. However, for patients with a BMI ≤ 21.0 kg/m2 and/or an ALB ≥ 36.4 g/L, we propose that therapeutic drug monitoring may assist in ensuring medication safety. Additionally, for the first time, a nomogram was developed to predict isavuconazole levels > 7 mg/L using BMI and ALB, though further validation is warranted.

Background: Comparative real-world data on the pharmacokinetics of once-daily tacrolimus formulations in de novo kidney transplantation remain limited. We compared tacrolimus exposure and dosing requirements with Envarsus and Advagraf during the early post-transplant period. Methods: We conducted a prospective, observational, single-center study including adult de novo kidney transplant recipients treated with once-daily tacrolimus as either Envarsus or Advagraf. The immunosuppressive protocol was based on thymoglobulin induction, with delayed initiation of tacrolimus at an initial dose of 0.15 mg/kg/day, prednisone, and sirolimus as the third immunosuppressive agent. Trough concentrations (C0), daily dose, and dose-normalized trough exposure (C0/D) were assessed at 48 h and over 3 months (days 7, 14, 30, 60, and 90). Dose adjustments were guided by therapeutic drug monitoring and Bayesian individualization to achieve target trough ranges (6–10 ng/mL during month 1; 5–7 ng/mL thereafter). Clinical effectiveness and safety outcomes were evaluated through month 3. Results: Ninety recipients were included (Advagraf n = 43; Envarsus n = 47). At 48 h, Envarsus achieved higher trough concentrations and higher C0/D than Advagraf (C0: 10.7 vs. 7.7 ng/mL; C0/D: 1.30 vs. 0.75 (ng/mL)/mg; both p &lt; 0.001). From week 1 to month 3, trough concentrations were similar between groups (week 1: 8.5 vs. 8.5 ng/mL, p = 0.968; month 3: 5.7 vs. 5.1 ng/mL, p = 0.234), but Envarsus required lower daily doses (week 1: 6.4 vs. 9.9 mg/day, p = 0.001; month 3: 3.2 vs. 4.1 mg/day, p = 0.021) and maintained higher C0/D (week 1: 1.53 vs. 1.00, p = 0.001; month 3: 1.94 vs. 1.57 (ng/mL)/mg, p = 0.012). At 48 h, infra-therapeutic troughs were less frequent with Envarsus (6.7% vs. 40.5%, p = 0.0001), while supra-therapeutic levels were more frequent (57.8% vs. 18.9%), and tacrolimus discontinuation due to high troughs occurred more often (23.4% vs. 7.0%, p = 0.032). Over 3 months, the proportion of measurements within the therapeutic range was similar (57.6% vs. 64.5%, p = 0.705). Efficacy and safety were similar between groups. Conclusions: In de novo kidney transplant recipients, Envarsus provides higher early tacrolimus exposure and consistently higher dose-normalized trough exposure than Advagraf, enabling lower maintenance doses while maintaining similar short-term effectiveness and safety. However, early overexposure was more frequent with Envarsus at 0.15 mg/kg/day, supporting careful early monitoring and consideration of lower starting doses.

An on-chip electromembrane extraction integrated with solid-phase microextraction (EME-SPME) was developed for the determination and monitoring of anticancer drugs, including imatinib, irinotecan, and mitomycin C, in various biological fluids. The extraction device incorporated an electrospun polyacrylonitrile (PAN)/MOF-303 nanocomposite fiber, which functioned as the extraction phase. Simultaneous analyte migration under an applied electric field and adsorption onto the nanocomposite surface enabled efficient preconcentration within the compact microfluidic platform. Under optimized conditions, the proposed EME-SPME-HPLC-UV method exhibited low limits of detection ranging from 0.1 to 1.5 µg L-1. Satisfactory linearity was achieved across the ranges 0.5-1000 ng mL-1 for imatinib and 5-1000 ng mL-1 for both irinotecan and mitomycin C, with coefficients of determination (R2) ≥ 0.9938. The method also demonstrated acceptable precision, with relative standard deviations (RSDs) ≤ 7.5%. The applicability of the system was investigated through the extraction of target analytes from human urine and plasma samples, yielding relative recoveries between 78 and 110%. These results highlight the potential of the developed EME-SPME platform as a sensitive, precise, and environmentally friendly technique for therapeutic drug monitoring of anticancer agents in complex biological matrices.

Lamotrigine is one of the most widely prescribed antiseizure medication (ASM) and mood stabilizer in the United States due to its favorable side-effect profile, lower risk of teratogenicity, and minimal drug-drug interactions. This study aimed to examine age- and sex-associated variability in prescribing and pharmacokinetics, focusing on postmenopausal women. Data were from electronic health records. Individuals were included if ≥18 years and received an ASM between January 1, 2015 and December 31, 2021. Lamotrigine prescriptions were compared based on age, sex, epilepsy diagnosis, and monotherapy/polytherapy. Statistical comparisons of proportions were conducted using two-proportion tests. To characterize age- and sex-related differences in LTG apparent oral clearance and assess the impact of covariates, linear mixed-effects modeling was employed. Records were available for 314 890 individuals, with 23 906 patients being prescribed lamotrigine at least once (as monotherapy or polytherapy) for both epilepsy and non-epilepsy diagnoses. The lamotrigine prescription rate was lower in postmenopausal women compared to younger women but higher than in older men, irrespective of diagnosis. Notably, lamotrigine was prescribed as monotherapy more frequently to patients without epilepsy than those with epilepsy, regardless of sex and age. The clearance of lamotrigine was 22% lower in postmenopausal women compared to younger women and 9% in older men. Lamotrigine clearance increased by 49% and 11% with co-administration of inducers or the presence of smoking, respectively. Lamotrigine clearance decreased by 51% in the presence of an inhibiting medication. Prescription rates for lamotrigine varied between patients with epilepsy and those with non-epilepsy conditions. Age and sex differences in pharmacokinetics suggest the need for lamotrigine dose adjustments, highlighting the importance of therapeutic drug monitoring in personalized epilepsy care. Lamotrigine use was less frequent in postmenopausal women compared to younger women but higher compared to older men. Postmenopausal women were prescribed lamotrigine as monotherapy to a lesser extent than younger women and older men.

To determine how certolizumab pegol (CZP) dose and dose adjustments influence CZP plasma trough levels to facilitate therapeutic drug monitoring of CZP. The effect of CZP dose and dose adjustments on CZP plasma trough levels was evaluated post hoc using longitudinal data from a 52-week randomized phase III trial (RAPID 1) and its open-label extension trial. Patients with active rheumatoid arthritis treated with methotrexate for ≥6 months were randomized to CZP 200 mg, 400 mg, or placebo every other week (EOW). Patients in the extension trial were initially treated with CZP 400 mg EOW, then reduced to 200 mg EOW after ≥6 months. Of 982 randomized patients, 846 patients entered the open-label extension trial. Median (interquartile range) plasma CZP concentrations after 12 weeks of treatment were 21.3 mg/L (14.7, 27.7) in the 200-mg group and 38.3 mg/L (29.2, 63.8) in the 400-mg group and increased from 18.3 (12.4, 26.5) to 43.4 (26.8, 63.3) mg/L after dose escalation from 200 to 400 mg EOW. Following CZP dose reduction from 400 mg to 200 mg, median CZP levels decreased from 36.1 (24.9, 49.0) to 17.2 (11.5, 23.1) mg/L. CZP plasma concentrations were influenced by both dose and dose adjustment in a predictable manner, with median plasma levels twice as high in the 400-mg group than in the 200-mg group, with a 2-fold increase after the dose increase from 200 to 400 mg. This facilitates the development of algorithms for therapeutic drug monitoring of CZP.

Therapeutic drug monitoring (TDM) is critical for optimizing drug efficacy and safety in precision medicine; however, conventional TDM methods rely on complex laboratory workflows. Consequently, there is an urgent need for fast, simple, and user-friendly technology to achieve point-of-care testing (POCT) for TDM. Aptamer-based sensors (aptasensors) have emerged as promising tools for point-of-care TDM because of their rapid response, high specificity, stability, and cost-effectiveness. This review summarizes the recent advances in aptasensor-based point-of-care TDM, analyzes current challenges, and explores future directions for enhancing clinical implementation. This comprehensive review examined aptasensor applications in TDM, emphasizing innovations in sensor design, detection limits, and real-world applicability across various drug types. The literature for this review was searched using PubMed, Web of Science, and Google Scholar, covering publications up to 2024. Search terms included "aptamer," "biosensor," and "drug monitoring." Relevant studies focusing on the application of aptasensors in point-of-care TDM were included and analyzed. Aptasensors have demonstrated significant potential for point-of-care TDM by offering rapid and accurate drug monitoring. However, key challenges including limitations in scalable fabrication processes, inadequate clinical validation in diverse populations, and environmental interferences affecting sensor robustness remain. Aptasensors hold a transformative potential for advancing point-of-care TDM, offering a pathway for personalized treatment optimization. Future efforts should prioritize rigorous clinical validation and improved stability in actual biological samples to fully realize their role in precision medicine.

Amikacin exposure and its association with ototoxicity and efficacy in nontuberculous mycobacterial pulmonary disease treatment.

Despite the general recommendation of AUC 0-24h /MIC ratio of 400-600 mg·h/L for vancomycin (VAN) effectiveness, there is no strong evidence of this index for patients undergoing renal replacement therapy (RRT). The aim of this scoping review was to summarize the scientific literature to assess the current evidence on VAN monitoring in hospitalized patients receiving intermittent hemodialysis (HD), identify gaps in knowledge, and guide future research. A systematic search was performed using PubMed, Web of Science, Embase, LILACS, and the Cochrane Library databases based on keywords related to VAN, dialysis, and Therapeutic Drug Monitoring (TDM). References in the articles were also screened. The inclusion criteria were studies involving hospitalized adults undergoing intermittent HD, receiving intravenous VAN therapy, and with available TDM data. Systematic searches retrieved 297 articles, of which 21 were selected along with 1 from the reference screening, for 22 included studies. Clinical outcome data are still insufficient to determine the best VAN TDM parameters for patients undergoing intermittent HD. Target attainment was suboptimal in most settings regardless of the TDM method. The intradialytic removal of VAN is highly variable because of the combination of the RRT modality, RRT parameters, and dialyzer characteristics, which are often poorly described. The exact influence of the RRT parameters on intermittent RRT settings remains unclear. The poor description of RRT, suboptimal VAN target attainment, and limited clinical outcome data in patients undergoing intermittent HD highlight the urgent need for further research. As VAN removal during RRT is influenced by a complex interplay of factors, improved dosing and monitoring strategies are required. In the future, model-informed precision dosing may play a significant role in optimizing VAN therapy in patients undergoing intermittent HD.

Dose adjustment of the anti-seizure medications levetiracetam and lamotrigine during the postpartum period. Schedule plan, safety and efficacy.

Tuberculosis (TB) treatment relies on a prolonged first-line antibiotic regimen, including isoniazid, rifampicin (RF), ethambutol (EMB), and pyrazinamide.Pharmacogenetics plays a crucial role in optimizing TB treatment by addressing individual variability in drug metabolism and responses. Genetic polymorphisms can significantly affect pharmacokinetics and therapeutic outcomes. The aim of this review was to explore the role of pharmacogenetics in first-line antibiotics used to treat TB. We reviewed the literature using PubMed, Scopus, Web of Science, and the Cochrane Library, focusing on articles published in the last 10 years (from December 2014 to December 2024) on the pharmacogenetics of first-line anti-TB drugs. Only English-language studies involving human subjects were included, prioritizing those investigating genetic variants that affect drug bioavailability. In this study, 33 manuscripts were included.N-acetyltransferase 2 Single-nucleotide polymorphisms were associated with different isoniazid acetylation rates, which affect toxicity and efficacy. Genetic variations in CYP2E1 , GSTM1 , and MnSOD also contribute to hepatotoxicity.For RF, variants in SLCO1B1 , ABCB1 , PXR , CAR , CES1 , and CES2 genes were related to variability in drug absorption, metabolism, and clearance, highlighting the need for personalized dosing strategies. Notably, SLCO1B1 rs4149056 polymorphism is associated with decreased OATP1B1 RF transport activity, potentially leading to increased plasma exposure, whereas other polymorphisms modulate drug exposure and clearance rates. In addition, sex, body weight, and genotype influenced RF pharmacokinetics, suggesting the need for tailored dosing recommendations based on patient characteristics.Similarly, variability in EMB pharmacokinetics is associated with CYP1A2 2159, which is related to a 50% reduction in bioavailability, necessitating dose adjustments in patients coinfected with TB and HIV. Some variants of ABCB1 , OATP1B1 , PXR , VDR , CYP24A1 , and CYP27B1 may further modulate the plasma and intracellular concentrations of EMB, thereby influencing drug efficacy. This review highlights the importance of integrating pharmacogenetic insights into clinical practice to enhance the efficacy of TB treatment, minimize toxicity, and prevent drug resistance. Despite promising evidence, further research and clinical validation are required to implement pharmacogenetics in routine TB management. Future advancements in therapeutic drug monitoring and omics technologies will pave the way for precision medicine in TB therapy.