This study was designed to investigate the impact of Lamotrigine (LTG) on astrocyte activation in epilepsy during pregnancy and to elucidate its potential underlying mechanisms. A rat model of epilepsy during pregnancy was established using pentylenetetrazole (PTZ) injection. CTX-TNA2 cells were treated with IL-1β to activate astrocytes. NLRP3 expression was modulated using NLRP3 inhibitor and pcDNA 3.1-NLRP3 overexpression. Neuronal damage, apoptosis, and astrocyte activation were evaluated by HE staining, TUNEL staining, and immunofluorescence, respectively. Levels of inflammatory cytokines were determined by ELISA. Protein and mRNA expression levels associated with inflammation and astrocyte activation were analyzed by Western blot and RT-qPCR. LTG significantly reduced the expression of NLRP3, TXNIP, and suppressed inflammatory responses. In vivo, LTG attenuated neuronal damage and apoptosis in the cerebral cortex and hippocampal CA1 region, accompanied by decreased levels of TNF-α, IL-1β, and IL-6, as well as reduced expression of GFAP, GLAST, and phosphorylated p65. Co-treatment with the NLRP3 inhibitor MCC950 further enhanced these effects. In vitro, LTG inhibited astrocyte proliferation and activation, whereas NLRP3 overexpression partially reversed these effects. LTG alleviates astrocyte activation and neuroinflammation in pregnancy-associated epilepsy, potentially through modulation of the NLRP3/TXNIP axis. These findings provide novel insights into the pathogenesis of epilepsy during pregnancy and suggest potential therapeutic strategies.

OBJECTIVE:To characterise meropenem pharmacokinetics in neonates and identify dosing regimens that optimize target attainment against common pathogens. METHODS:This retrospective dual-centre cohort study analysed opportunistic meropenem plasma concentrations measured using a validated HPLC-MS/MS method. Neonates with severe renal impairment were excluded. A population pharmacokinetic model was developed and externally validated. Monte Carlo simulations were used to evaluate the probability of target attainment and cumulative fraction of response (CFR) for traditional simple/prolonged-infusion (TSPI) and optimised two-step administration therapy (OTAT) regimens. RESULTS:The analysis included 114 neonates. A one-compartment model with first-order elimination best described the data. Body weight at admission (WT) was a significant covariate for both clearance (CL) and volume of distribution (Vd), while congenital heart disease (CHD) was a significant covariate for clearance. Typical CL and Vd were 0.175 L/h and 0.403 L, respectively. External validation showed satisfactory predictive performance. For the aggressive target (100% f T > MIC), TSPI often required high doses (≥ 30 mg/kg every 8 h). All evaluated OTAT regimens (20 mg/kg per dose every 8-12 h) were predicted to achieve CFR ≥ 90% for both targets across the evaluated pathogens. Simulated steady-state peak concentrations increased with the bolus fraction; therefore, the 5 mg/kg bolus followed by infusion of the remaining 15 mg/kg was selected as the preferred OTAT regimen to limit unnecessary peak exposure. CONCLUSIONS:WT and CHD significantly influence meropenem pharmacokinetics in neonates. The 5 + 15 mg/kg OTAT regimen may provide a model-informed alternative to empirical dose escalation. Prospective clinical evaluation is warranted.

BACKGROUND:Ulcerative colitis (UC) is chronic inflammatory bowel disease that significantly impairs both physical and psychological well-being. This study explores the prevalence of depression and its impact on quality-of-life (QoL) among UC patients in Pakistan, aiming to inform integrated care approaches in a setting where mental health often remains under-addressed. METHODOLOGY:A cross-sectional study was conducted at outpatient IBD clinics of Gastroenterology department of Holy Family Hospital, Rawalpindi, from February 2024 to May 2025. Data were collected using structured forms covering demographics, clinical history, and disease severity (assessed via Mayo Score and Montreal classification). Psychological status was evaluated using HADS and BDI-II, while QoL was assessed using the IBDQ-32. RESULT:Among 101 UC patients, anxiety was present in 21.8% and depression in 17.8% patients. The mean IBDQ score was 150 ± 32.9, with 12.9% reporting poor QoL, 60.4% good QoL, and 1% excellent QoL. Disease severity showed significant positive correlations with anxiety (ρ = 0.42,p = 0.001) and depression (ρ = 0.38,p = 0.002), and strong negative correlation with QoL (ρ = -0.51,p < 0.001). Kruskal-Wallis tests confirmed significant differences in psychological distress and QoL across severity groups (p < 0.05). Multivariable regression identified Mayo score, HADS-A, HADS-D, and disease extent as significant negative predictors of IBDQ score (p < 0.05). CONCLUSION:This study underscores strong correlation between higher Mayo scores, together with elevated levels of anxiety and depression, and poorer QoL as measured by IBDQ among patients with UC in Pakistan. Therefore, there is an important consideration to explore the psychological burden and QoL impairments faced by UC patients in Pakistan to inform holistic management strategies.

Eravacycline is a fully synthetic, fluorinated third-generation tetracycline with broad-spectrum antibacterial activity, approved for the treatment of complicated intra-abdominal infections(cIAI). Clinical studies have demonstrated favorable safety and predictable pharmacokinetic properties, supporting its use in diverse complicated infections. With increasing application in critically ill patients and those with significant organ dysfunction, increasing attention has been directed toward the potential alterations in pharmacokinetics caused by pathophysiological changes in these populations. Such variability may influence drug exposure and treatment outcomes; however, current dosing strategies largely follow standard recommendations, and evidence supporting dose optimization in special populations remains limited. This review provides a comprehensive overview of current evidence regarding the chemical structure, antimicrobial and pharmacological properties, pharmacokinetics, pharmacokinetic/pharmacodynamic characteristics, clinical applications, population pharmacokinetics, and therapeutic drug monitoring of eravacycline, aiming to support rational clinical use and individualized dosing strategies.

BackgroundPD-1/PD-L1 inhibitors combined with chemotherapy have improved survival outcomes in patients with driver mutation–negative non-squamous non-small cell lung cancer (non-sqNSCLC). However, the comparative efficacy, safety, and economic value of available PD-1/PD-L1 inhibitor–based regimens remain uncertain in China.MethodsWe conducted a network meta-analysis to indirectly compare the efficacy and safety of 14 first-line treatment regimens, including 13 PD-1/PD-L1 inhibitor–based chemotherapy regimens and chemotherapy alone, in patients with driver mutation–negative non-sqNSCLC. Clinical evidence was subsequently integrated into a Markov model with a 10-year time horizon and 3-week cycles to evaluate cost-effectiveness from the perspective of the Chinese healthcare system. Transition probabilities were derived from reconstructed survival curves using parametric survival models. The primary economic outcomes included total costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). Deterministic and probabilistic sensitivity analyses were performed to assess model robustness.ResultsThe network meta-analysis demonstrated that toripalimab, sintilimab, and pembrolizumab combined with chemotherapy provided superior efficacy and favorable safety among 13 PD-1/PD-L1 inhibitors with chemotherapy for non-sqNSCLC. In the cost-effectiveness analysis, toripalimab with chemotherapy achieved 2.583 QALYs at a total cost of $39,232.33. And it was cost-effective compared with chemotherapy alone, camrelizumab-, tislelizumab-, and sintilimab-based chemotherapy regimens, with ICERs ranging from $10,624.47 to $16,120.12 per QALY, all below the willingness-to-pay threshold of $41,859/QALY. Compared with chemotherapy alone, camrelizumab, tislelizumab, sintilimab with chemotherapy were cost-effective, with ICERs of $28,813.78/QALY, $19,278.47/QALY, and $20,315.01/QALY, respectively. PFS and PD utilities were key drivers of cost-effectiveness, while drug costs predominantly influenced regimens with ICERs.ConclusionAmong currently available first-line treatment strategies for driver mutation–negative non-sqNSCLC in China, toripalimab and sintilimab combined with chemotherapy demonstrated favorable clinical and economic profiles. These findings provide evidence to support treatment selection, reimbursement decisions, and healthcare resource allocation in clinical practice.

Health literacy (HL) is a critical determinant of health outcomes, influencing individuals' ability to understand health information, make informed decisions, and engage in self-care practices. By understanding the comparisons of HL levels, healthcare providers can develop targeted interventions. This study investigates the determinants of HL levels among patients who visit community pharmacies, specifically in Gujrat and Islamabad, Pakistan, to identify factors associated with low HL. A cross-sectional study using the European Health Literacy Survey Questionnaire (HLS-EU-Q) was conducted to assess patients' demographic and socioeconomic characteristics and their HL levels. Spearman correlation analyses and multiple regression models explored the relationship between HL and its determinants. The study revealed that 61.3% of participants in Gujrat were male, compared to 52.7% in Islamabad, with the largest age group being 18−25 years (31%) in Islamabad versus 18% in Gujrat. HL was problematic in both regions, with 74% in Gujrat and 60% in Islamabad experiencing inadequate or problematic levels. Age, financial status, education, and social status were positively correlated with HL, while gender, part-time employment, and unemployment were negatively correlated. Frequent healthcare visits were associated with lower HL in Gujrat, while higher degrees and social status were associated with higher HL. It was concluded that the prevalence of inadequate HL is higher in Gujrat and is associated with factors such as challenges in understanding healthcare, disease prevention, and health promotion, compared to Islamabad. Our findings not only advance understanding of HL in Pakistan but also provide evidence to inform cost-effective public health strategies and policies aimed at reducing healthcare inequities, improving medication adherence, and optimising resource utilisation.

Predicting vancomycin exposure is essential for optimizing dosing regimens in sepsis patients. While population pharmacokinetic (PPK) models are commonly used, their performance is limited. Machine learning (ML) models offer advantages over PPK models, but it remains unclear which model-PPK, Bayesian, ML, or hybrid PPK-ML-is best for predicting vancomycin exposure across different clinical scenarios in sepsis patients. This study compares the performance of these models in predicting the 24 hour area under the blood concentration curve (AUC24) to support precision dosing in sepsis care. Data from sepsis patients treated with intravenous vancomycin were sourced from the MIMIC-IV database. The data set was split into training and testing sets, and four models-PPK, Bayesian, ML, and hybrid-were developed. In the testing set, AUC24 was predicted using all models, and performance was evaluated using mean absolute error, mean squared error, root mean squared error, mean absolute percentage error (MAPE), and R². A total of 4,059 patients were included. In the absence of vancomycin concentration data, the hybrid model outperformed both PPK and Bayesian models, with MAPE improvements of 58% and 17%, respectively. When vancomycin concentration data were available, the Bayesian model demonstrated the best performance (MAPE: 13.37% vs 68.17%, 34.17%, and 28.52% for PPK, Random Forest, and hybrid models). The hybrid model is recommended to predict AUC24 when concentration data were unavailable, while the Bayesian model should be used when concentrations were available, offering robust strategies for precise vancomycin dosing in sepsis patients. IMPORTANCE:This study evaluates and compares the performance of four models-PPK, Bayesian, ML, and hybrid PPK-ML-in predicting vancomycin exposure (AUC24) in sepsis patients using real-world data from the MIMIC-IV database. These results underscore the importance of selecting appropriate models based on the availability of concentration data, providing valuable guidance for precision dosing strategies in sepsis care. This work contributes to advancing personalized vancomycin therapy, optimizing dosing regimens, and improving clinical outcomes in sepsis patients.

Letermovir (LMV) is vital for cytomegalovirus prevention in transplant recipients, but its safety and drug-drug interactions (DDI) related adverse event (AE) risks require further investigation. This study conducted a pharmacovigilance analysis to identify novel AE signals of LMV and assess DDI-related AEs with commonly co-administered drugs. AE reports from 29 quarters, from the launch of LMV to the fourth quarter of 2024, were collected from the Food and Drug Administration Adverse Event Reporting System for analysis. Two statistical models (reporting odds ratio [ROR] method and medicines and healthcare products regulatory agency) were used to identify AEs meeting the threshold, which were then compared with LMV drug labels and designated medical event (DME) risk signals. Four models were applied to detect potential AE signals related to LMV combination use, and DDI-related AEs and DMEs were analyzed in conjunction with single-drug mining results. Finally, 54 LMV AE signals were identified, of which 4 AE signals had appeared in the LMV drug labels, namely edema (ROR = 3.69), acute heart failure (ROR = 14.48), pericardial effusion (ROR = 4.77), and atrial fibrillation (ROR = 3.61). Among the remaining new AE signals, AEs with stronger ROR values included herpetic gastritis (ROR = 23,772.49), human herpesvirus 6 encephalitis (ROR = 214.17), and acute graft-versus-host disease (aGVHD) in skin (ROR = 190.2). Eight DME signals of LMV were determined, such as hepatic failure, drug-induced liver injury, renal failure, and acute kidney injury (AKI). In the DDI analysis, 279 DDI-related AE signals meeting all four model criteria were identified. Among 28 drugs commonly co-administered with LMV, immunomodulatory agents contributed the highest proportion of signals (34.4%, 96/279), with cyclosporine associated with the most AE types (10.4%, 29/279). The most frequent AEs included aplastic anemia (4.3%), esophagitis (3.9%), and renal failure (3.6%). There was a positive AE signal difference when LMV was combined with cyclosporine or tacrolimus. When used in combination with cyclosporine, in addition to cardiac events and peripheral edema listed in the LMV drug label, DME signals such as pancytopenia, febrile neutropenia, AKI, and hepatic failure may also occur; when used in combination with tacrolimus, one needs to be alert to the occurrence of aGVHD in skin/intestine. LMV use may induce cardiac AE signals such as acute heart failure, pericardial effusion, and atrial fibrillation, and may increase the risk of herpes virus reactivation. When LMV is used in combination with drugs such as cyclosporine or tacrolimus, it may exacerbate hepatic and renal toxicity. Acute heart failure and atrial fibrillation AE signals were detected when combined with cyclosporine. Future efforts should focus on the safety of LMV in clinical practice and real-world settings, with optimized medication strategies to minimize risks and enhance therapeutic outcomes.

This study aims to assess the applicability of published polymyxin B population pharmacokinetics (PopPK) models in critically ill patients using an external dataset, with the goal of establishing an evidence-based framework to guide optimal model selection for precision dosing in clinical critical care practice. Nine published PopPK models of polymyxin B were reconstructed. A validation dataset was compiled from data of critically ill patients receiving intravenous polymyxin B. The predictive performance was assessed based on predicted and simulated diagnosis and Bayesian forecasting. The data from 132 samples of 72 critically ill patients were collected as the validation dataset. In prediction-based diagnostics, none of the nine PopPK models met the criteria. In simulation-based diagnostics, although no model achieved full adequacy in the tests, four models showed acceptable normality in normalized prediction distribution error plots. Bayesian forecasting significantly improved the predictive performance across all models, particularly when ≥ 2 prior observations were available. Collectively, one model demonstrated good prediction performance. The integration of PopPK model with Bayesian forecasting provides a valuable approach for model-informed precision dosing of polymyxin B, facilitating the individualization of dosing regimens in critically ill patients.

Objective Methicillin-resistant Staphylococcus aureus (MRSA) infections among children are escalating annually. Vancomycin stands as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window for vancomycin in pediatric patients remains a challenge. Methods This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients. Results A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration ( C min ) of vancomycin was 7.6 ± 5.5 mg/L. 74.3% of patients exhibited concentrations below the conventionally recommended therapeutic window of 10-20 mg/L. Patients responding positively to treatment exhibited significantly higher C min values (8.4 ± 5.7 mg/L) compared to those with treatment failure (5.9 ± 4.4 mg/L, P = 0.006). Similarly, patients who developed nephrotoxicity had significantly elevated C min levels (17.8 ± 5.3 mg/L) compared to those without nephrotoxicity (6.4 ± 3.9 mg/L, P < 0.001). Both univariate and multivariate logistic regressions revealed that the C min of vancomycin was the predictor of both clinical outcomes and adverse reaction. Furthermore, receiver operating characteristic curve analysis pinpointed that C min of vancomycin with 5.9 mg/L and 14.8 mg/L associated with clinical effectiveness and safety, respectively. Referring to the therapeutic window of adults, vancomycin underexposure in pediatrics is serious extremely. Conclusion Based on our findings, we propose a revised therapeutic window of 5.9-14.8 mg/L for vancomycin in pediatric patients, which could aid in optimizing treatment outcomes and minimizing adverse effects.

To explore the efficacy and safety of non-carbapenem-containing (NCC) regimens and carbapenem-containing regimens (CC) regimens, along with the factors influencing the outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia. This study retrospectively enrolled critically ill patients with CRAB pneumonia who were treated with NCC and CC regimens in a teaching hospital. The primary efficacy outcome was the 28-day clinical efficacy rate, and the safety outcome was the incidence of nephrotoxicity. After the propensity score matching analysis removed the differences between the two groups, the differences in outcomes were statistically analyzed. Cox regression and logistic regression models were used to analyze the factors influencing the outcomes of critically ill patients with CRAB pneumonia. Data from 168 critically ill patients with CRAB pneumonia were eventually included in this study for analysis (NCC = 84, CC = 84). The 28-day clinical efficacy rate was significantly lower in the CC group compared to the NCC group (40.5

BackgroundPolymyxin B sulfate (PBS) and colistin sulfate (CS) are the last-line treatments for infections caused by multidrug-resistant Gram-negative bacteria, but their efficacy and safety have not been validated. The aims of the current study were to (1) determine their efficacy and safety among critically ill patients and the influencing factors, and (2) determine the relationships of drug exposure with efficacy and safety, to provide evidence for the precision dosing.MethodThis retrospective study included 100 critically ill patients treated with PBS and 80 treated with CS. The efficacy outcomes were clinical efficacy and 30-day mortality, while the safety indicator was acute kidney injury (AKI) incidence.ResultThere was no significant difference between the two drugs in clinical efficacy, 30-day mortality, or overall AKI incidence, but the incidence of stage 3 AKI was significantly higher in the PBS cohort than the CS cohort. Therapeutic drug monitoring (TDM) and trough concentration (Cmin) were significantly associated with clinical efficacy and AKI in both cohorts. Classification and regression tree analysis revealed that Cmin values of ≥0.91 mg/L for PBS and Cmin ≥ 0.53 mg/L for CS were associated with higher clinical efficacy.ConclusionThere is basically no significant difference in the efficacy and safety of PBS and CS. TDM can significantly improve the clinical efficacy of both drugs and reduce the incidence of AKI. TDM is therefore recommended to improve the clinical efficacy while reducing the adverse reactions.

Based on the high expression of folic acid (FA) receptors in triple-negative breast cancer cells, we encapsulated licochalcone A (LCA) in FA-modified polyethylene glycol-poly(lactic-co-glycolic) acid nanoparticles (NPs) for enhanced targeting and antitumor activity. In vitro experiments on 4T1 cells showed that NPs with FA modification exhibited excellent performance, including inhibition of cell proliferation, reduction of 50% inhibitory concentration values of LCA, and activation of reactive oxygen species production, thereby inhibiting cell proliferation. This drug delivery system promotes drug uptake by tumor cells and significantly improves drug delivery efficiency. Regarding relevant in vivo experiments in tumor-bearing mice, we further demonstrated that NPs with FA modification have significant tumor-targeting effects, as shown by drug penetration and small animal imaging experiments. Target-modified NPs loaded with LCA significantly inhibited tumor growth and prolonged survival in mice. Histological analysis further demonstrated the positive effect of the preparation in reducing lung and liver metastasis lesions. Our study highlights that FA-modified NPs can effectively deliver LCA to the tumor site, enhancing the potential application of LCA to inhibit tumor proliferation and metastasis, and providing new strategies and possibilities for treating triple-negative breast cancer.

Methicillin-resistant Staphylococcus aureus (MRSA) infections among children are escalating annually. Vancomycin serves as the frontline therapeutic agent against MRSA infections. However, determining the therapeutic window that maximizes efficacy while minimizing the risk of toxicity for vancomycin in pediatric patients remains a challenge. This study aimed to explore a therapeutic window for vancomycin in pediatric patients. This retrospective study collected data from hospitalized children aged 1 month to 18 years, who underwent routine therapeutic drug monitoring for vancomycin. We analyzed the distribution patterns of vancomycin concentrations in these patients. Factors influencing clinical outcomes and adverse reaction (nephrotoxicity) were investigated. ROC analysis was used to establish the therapeutic window for vancomycin in pediatric patients. A comprehensive dataset encompassing 183 pediatric patients with 330 samples was analyzed. The mean trough concentration (Cmin) of vancomycin was 7.6 ± 5.5 mg/L. 74.3

Therapeutic drug monitoring (TDM) enables the personalization of treatment regimens, enhancing efficacy in combating infectious diseases while minimizing toxicity risks and reducing the potential for pathogenic resistance. However, existing TDM techniques still present certain limitations. Chromatographic analysis involves a prolonged detection period, which hampers its capacity for rapid multi-sample analysis. Immunoassay is constrained by poor specificity and stability, as well as a restricted range of detectable drugs. Surface-enhanced Raman spectroscopy (SERS) amplifies the Raman signals of target molecules via the local electromagnetic field and charge transfer effects on the surface of plasmonic materials, offering many significant advantages including high sensitivity, rapid detection, minimal sample requirements, and the ability to provide molecular fingerprints. SERS biosensing has demonstrated considerable potential in the field of blood drug concentration monitoring. This paper comprehensively reviews the research on the application of SERS in the TDM of antimicrobial agents. Beginning with the clinical practice of antimicrobial TDM, this review systematically introduces the principles of SERS techniques, the enhancement substrates, and the commonly used data processing methods including machine learning. It then provides a detailed discussion of the application of SERS in the TDM of various types of antimicrobials. Finally, it summarizes four major challenges currently faced by SERS techniques in antimicrobial TDM-namely protein corona effects, matrix interferences, substrate heterogeneity, and quantification reproducibility-and proposes potential future directions. This paper aims to offer new strategies and perspectives for the TDM and personalized dosage of antimicrobial agents.

Liver injury severely limits the clinical use of voriconazole. Clarifying the mechanism and markers of voriconazole-induced liver injury is of great significance. In this study, a quantitative systems toxicology model of voriconazole-induced liver injury was constructed through integrating the mechanism-based hepatoxic parameters generated from in vitro assays into a self-built physiologically based pharmacokinetic model. The hepatotoxic substances, main mechanism, dose correlation and markers of voriconazole-induced liver injury were determined according to liver injury incidence of simulated populations. The voriconazole-treated mice, voriconazole or voriconazole N-oxide (VNO)-treated HepG2 were used to validate the relationship of liver injury with oxidative stress and VNO. The results demonstrated that the incidence of voriconazole-induced liver injury was 17.9 %, which was dose-dependent. VNO-induced oxidative stress contributed most to liver injury, which was manifested by reactive oxygen species (ROS) accumulation and antioxidant enzymes inhibition. Liver ROS/reactive nitrogen species baseline clearance Vmax and antioxidant enzymes activities were negatively correlated to plasma liver function indicators elevation and liver adenosine triphosphate loss. We concluded that VNO-induced oxidative stress was the main cause of voriconazole-induced liver injury, and basic antioxidant capability indicators might be potential markers. This study may provide new insights for mechanism understanding and early warning of voriconazole-induced liver injury.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug–drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.

ABSTRACT The rational use of medications is essential for optimal healthcare delivery, especially in developing countries. This research delves into prescribing patterns within the healthcare system of Pakistan and Yemen against World Health Organization (WHO) prescribing indicators to uncover variances from recommended practices. A cross‐sectional study was conducted in the outpatient department of different hospitals in Pakistan and Yemen, including 400 prescriptions. Demographic details and prescription data were collected, focusing on WHO prescribing indicators including the average number of drugs per encounter, the percentage of drugs prescribed by generic name, the percentage of drugs prescribed from the essential drug list, and the prevalence of antibiotic and injectable prescriptions. The mean age of patients was 43.54 ± 16.92 and 38.81 ± 18.67 years in Pakistan and Yemen, respectively. Polypharmacy was observed in both populations, with an average of 5.44 ± 1.16 drugs per encounter in Pakistan and 6.18 ± 1.09 in Yemen. Irrational antibiotic use was observed, with rates of 65% and 72.5% encounters in Pakistan and Yemen, respectively. The mean injectable medications per hospital were 28.5 (57%) and 34 (68%) in Pakistan and Yemen, respectively. In Pakistan, the mean percentage of generic prescribing was 74.18%, while in Yemen, it was 78.24%. The total percentage of drugs prescribed from the essential drug list was 98.24% in Pakistan, whereas 97.87% in Yemen. The findings reveal significant deviations from WHO prescribing indicators marked by polypharmacy and excessive antimicrobial and injectable utilization, which pose risks to patient safety and contribute to antimicrobial resistance.