搜索结果：Therapeutic drug monitoring

Lithium is an effective mood stabilizer with a narrow therapeutic range. Lithium-associated adverse drug reactions affect multiple body systems and can result in significant morbidity and death. In this study, we aim to determine the severity, outcomes, and preventability of lithium-associated adverse drug reactions. We conducted a retrospective cross-sectional study of lithium-associated adverse drug reaction patients, who visited a tertiary-care university hospital between 2012 and 2022, and had lithium levels beyond the therapeutic range. Patients with the following conditions were excluded: intentional ingestion, incomplete medical records, and no lithium-associated adverse drug reaction. Data were collected from the hospital's database and reviewed by three independent reviewers. Adverse drug reaction preventability was assessed using a Likert scale (non-preventable: 1-3, preventable: 4-6). Characteristics, clinical presentation, and severity of adverse drug reactions were analyzed. A total of 91 patients were included: 32 (35.2%) and 59 (64.8%) in the non-preventable and preventable groups, respectively. The patients in the preventable group were older (P&#x2009;=&#x2009;0.017), had lower estimated glomerular filtration rates (eGFRs; P&#x2009;<0.001), and had more comorbidities (diabetes, hypertension, and dyslipidemia; P&#x2009;=&#x2009;0.004). The patients primarily presented in the outpatient department (63.74%) and had acute-on-chronic onset (45.1%). Preventable adverse drug reactions were linked to delayed monitoring (55.9%), dehydration (39.0%), drug interactions (17.0%), previous episode of high lithium levels within three years (13.6%), and clinical underdetection (11.9%). The most common cause of non-preventable adverse drug reactions was lithium dose adjustment (37.5%). Neurological effects were predominant. There were significantly more moderate (47.5%) and severe (5.1%) cases in the preventable group than non-preventable group (18.8% moderate, and no severe case; P&#x2009;=&#x2009;0.006). The majority of lithium-associated adverse drug reactions are preventable and linked to greater severity. Targeted interventions should focus on older patients with renal impairment, or comorbidities. Clinical strategies should prioritize regular lithium monitoring, proactive drug-interaction screening, and patient education regarding hydration to reduce these preventable adverse drug reactions. Our findings indicate that most lithium-associated adverse drug reactions are preventable and influenced by several factors (e.g., age, eGFR, comorbidities, drug interactions, and dehydration) and that preventable adverse drug reactions result in more severe outcomes.

Continuous monitoring of drug dynamics directly in living tissue remains a major challenge, notably in the brain, where the blood-brain barrier creates distinct microenvironments. Here, we report an implantable fiber optic surface plasmon resonance (FO-SPR) biosensor coated with aptagel, a split-aptamer-crosslinked hydrogel, for continuous monitoring of a small-molecule drug, vancomycin. The aptagel undergoes analyte-induced volumetric and refractive index changes, providing a self-contained means for reversible, label-free optical detection via shifts in the SPR wavelength (&#x3bb;SPR) while ensuring sensor stability in complex physiological matrices. The sensing area was miniaturized to 3 mm2 (3 mm length, 300 &#x3bc;m diameter) for cortical implantation while maintaining sensitivity of >2000 nm/RIU. The sensor performed consistently in vitro across diverse biological media, including blood serum, with detection limits of 1.7-2.5 &#x3bc;M. Upon implantation into the rat cortex, time-resolved &#x3bb;SPR signals were recorded over several hours after intravenous vancomycin administration, representing to our knowledge the first demonstration of plasmonic fiber-based monitoring of a small-molecule drug directly in brain tissue. Baseline-corrected shifts (&#x394;&#x3bb;SPR) captured in vivo drug dynamics, with a consistent absorption phase but with inter-animal variability in peak amplitude and clearance kinetics. This work establishes a proof-of-concept platform for continuous optical monitoring in deep tissue and highlights the potential of FO-SPR sensing for in vivo pharmacokinetic applications.

Narrow therapeutic index drugs (NTIDs) require precise monitoring to ensure efficacy and prevent toxicity, yet their analysis in complex biological matrices remains challenging. This study presents a novel sonic-spray ionization mass spectrometry (SSI-MS) method for the rapid and sensitive analysis of NTIDs, using tacrolimus as a model compound. The custom-built SSI source operates without high voltage or heating, relying solely on a coaxial nitrogen flow for gentle and efficient ionization. Under optimized conditions, the method achieved a low limit of quantitation (5 ng/mL) and excellent linearity (R&#xb2; = 0.999) across the clinically relevant therapeutic window (5-200 ng/mL). Compared to electrospray ionization, SSI provided a cleaner background and a 1.88-fold improvement in the signal-to-noise ratio. The accuracy of this method was validated in mice serum, with recoveries ranging from 99.8% to 106.8% and relative standard deviations below 8.4%. Furthermore, the platform successfully detected tacrolimus directly in a saline matrix. These results demonstrate that SSI-MS is a powerful, high-performance tool for the rapid and reliable quantification of NTIDs, offering significant potential for advancing therapeutic drug monitoring in clinical practice.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in immunocompromised patients, particularly transplant recipients. The emergence of drug-resistant CMV strains and the toxicities of conventional antiviral therapies like ganciclovir highlight the need for novel treatments. Maribavir, a benzimidazole riboside, offers an alternative due to its unique mechanism of action-selectively inhibiting the CMV UL97 protein kinase, which is essential for viral replication. It is effective against wild-type and ganciclovir-resistant CMV strains. Pharmacologically, maribavir is rapidly absorbed, highly protein-bound (>98%), and metabolized via CYP3A4, leading to a short half-life (4-5 hours) and twice-daily dosing. However, CYP3A4-mediated drug-drug interactions (DDIs)-particularly with inducers like rifampin-pose a risk, as rifampin reduces maribavir's Cmax, AUC, and Ctrough by 39%, 60%, and 82%, respectively, potentially compromising efficacy. A 47-year-old renal transplant patient with ganciclovir-resistant CMV and concurrent tuberculosis required maribavir and rifampin. Despite the DDI, dose escalation to 800 mg TID (guided by therapeutic drug monitoring) achieved adequate Ctrough, controlling CMV viremia without adverse effects. This case suggests that dose adjustment with close monitoring may mitigate DDIs when coadministration is unavoidable. Further studies are needed to validate this approach, given the increased cost and potential for resistance.

Drug-induced suicidality is a severe and frequently overlooked area within pharmacovigilance. While the traditional focus has centered on psychotropic medications, non-psychotropic drugs acting on histamine receptors may also induce depression and suicidality through central nervous system effects. A 33-year-old male presented with a chief complaint of "dizziness for 1 week." His dizziness improved after taking a betahistine hydrochloride oral solution, but he subsequently developed symptoms including low mood, emotional detachment, and suicidal ideation. Given the close temporal relationship between drug intake and symptom onset, rapid improvement after withdrawal, and assessment by the Naranjo scale and World Health Organization-Uppsala Monitoring Centre system, the depressive symptoms with suicidality were preliminarily judged to be "probable" betahistine-associated adverse reactions (grade 1 [mild]). Betahistine was discontinued immediately and replaced with difenidol hydrochloride tablets to manage the dizziness. Suicidal ideation resolved completely within 2 days of betahistine discontinuation. No recurrence of psychiatric symptoms was reported during the 3-month follow-up period. This case emphasizes the need for clinicians and pharmacists to move beyond the cognitive bias that only psychotropic drugs carry a significant suicide risk. Vigilance for potential neuropsychiatric adverse reactions, such as depression and suicidality, should be maintained for all drug classes, particularly for non-psychotropic agents acting on histamine receptors. Timely recognition and drug discontinuation are crucial to ensure patient safety.

Benin has adopted the WHO 2019 recommendations by integrating dolutegravir into the first- and second-line treatment regimen with regular monitoring of the emergence of resistance. The standard of care document has been updated, and healthcare staff have been trained on dosage, drug interactions, and the management of adverse effects. The patient, diagnosed as HIV-1 positive, was started on antiretroviral therapy, which had to be modified due to poor adherence. HIV-RNA was extracted from plasma with QIAGEN RNA kit, and nested polymerase chain reaction was performed in Reference National Laboratory of Health Program Fighting Against AIDS in Benin on the polymerase gene using the Applied Biosystems HIV-1 Genotyping Kit PR-RT with Integrase. Drug resistance mutations and the remaining effective antiretrovirals drug were identified using Stanford University Antiretroviral-Associated Resistance Mutation Interpretation Algorithm (https://hivdb.stanford.edu/ Version 9.8). The phylogenetic tree was constructed using SeaView with the maximum likelihood method and 1000 bootstrap iterations to identify the viral subtype along PR-RT and integrase gene. No PI-associated resistance mutations were observed. The NRTIs and NNRTIs associated resistance mutations were (M41&#x2009;ML, D67G, S68G, K70R, M184&#x2009;V, T215F, and K219E), (V179E and Y188&#x2009;L), respectively. The major and accessory INSTI mutations observed were (E138&#x2009;K, G140&#x2009;GA, S147SG, Q148R, and N155H) and T97A, respectively. All protease inhibitors were effective against the identified HIV-1 viral strain which was a CRF02_AG along the polymerase gene. HIV-1 resistance genotyping can improve monitoring of the emergence of resistance in nonadherent individuals and anticipate early treatment failures in order to accelerate access to the third 95 of UNAIDS 95-95-95 target.

Azithromycin is beneficial in a multitude of respiratory diseases; however, its effects on both subjective and objective measures of cough have been less extensively studied. Traditional 24-h cough counting assessments are highly variable, potentially underestimating the antitussive effect of therapeutics. Patients with asthma, COPD, interstitial lung disease and refractory chronic cough who reported cough as the predominant symptom were continuously monitored using a smart watch equipped with Hyfe cough detection software. Patients were monitored 1&#x2005;week prior to and 4&#x2005;weeks after commencing azithromycin. Participants were also assessed using patient-reported outcome measures and a 4-week daily cough visual analogue scale diary. Cough data were analysed using the novel cough metrics "relief of cough" and "cough density". 30 participants with a broad range of respiratory diseases were recruited; 80% (n=24) had satisfactory usage of the cough monitor (>12&#x2005;h&#xb7;day-1 for 90% of study days). There was a significant reduction in the geometric mean of coughs per hour from pretreatment baseline to follow-up at week 4 (11.4 versus 7.5&#x2005;coughs&#xb7;h-1, p=0.026). This reduction was observed after 1&#x2005;week and cough counts reduced progressively from week 1 to week 4. Of the 24 participants who had adequate cough monitoring, 29% (n=7) had a >50% reduction in cough frequency. The mean proportion of time that participants had relief of cough improved between baseline and follow-up (74% versus 81%, p<0.001). There was no significant difference in cough density metric (47.5 versus 42.8, p=0.069). Significant improvements were observed in all patient-reported outcomes. This is the first study to assess the antitussive effect of a drug using continuous cough monitoring. Further trials should use this method of cough assessment to obtain a more granular assessment of cough in airways diseases.

Relapsed/metastatic anaplastic thyroid carcinoma (R/M ATC) is associated with poor prognosis. Approximately 40% of ATCs harbor the BRAFV600E mutation, for which targeted therapy is available. However, the clinical characteristics of BRAFV600E-mutant versus wild-type ATC and the role of liquid biopsy (LB) for molecular assessment and monitoring remain incompletely defined. Consecutive patients with R/M ATCs treated at a tertiary referral center were stratified as BRAF wild-type (Cohort A) or BRAFV600E-mutant (Cohort B). Patients received chemotherapy, dabrafenib and trametinib (BRAF/MEKi), immune checkpoint inhibitors (ICI) or best supportive care. Tumor tissue (TB) was analyzed by RT-PCR and/or next-generation sequencing (NGS). Circulating cell-free DNA was assessed by droplet digital PCR (ddPCR) and/or a 52-gene NGS panel on LB at baseline in both cohorts and longitudinally in Cohort B. Clinical characteristics, treatment outcomes, and concordance between TB and LB were evaluated. Between 2018 and 2021, 24 patients were included (13 Cohort A, 11 Cohort B). BRAFV600E tumors more frequently presented with metastatic disease at diagnosis (81.8% vs. 15.4%, p&#x2009;=&#x2009;0.003). Overall, 79% received first-line therapy and 41.6% second-line treatment. All patients in Cohort B received BRAF/MEK inhibitors, achieving a median progression-free survival of 3.2 months (95% CI 1.2-17.5). Concordance for BRAFV600E status between TB and LB assessed by ddPCR was 93.7% (specificity 100%, sensitivity 85.7%). Among 12 paired TB/LB NGS analyses, overall mutation concordance was 30%. In longitudinal assessment, LB anticipated disease progression in 3 of 6 cases and, in one case, identified emerging secondary alterations during BRAF/MEK inhibitor therapy. BRAFV600E-mutant ATC displays distinct clinical features and improved survival when treated with targeted therapy; ddPCR-based liquid biopsy provides a rapid and sensitive method for BRAFV600E detection and may support timely therapeutic decision-making. Serial LB analysis may contribute to disease monitoring and detection of resistance mechanisms in selected patients.

The safety of drug-eluting stents (DES) in patients undergoing percutaneous coronary intervention (PCI) remains largely lacking in China. This study aimed to determine the 1-year adverse outcomes in a large registry of patients undergoing PCI with DES for coronary artery disease (CAD) in China. We also examined clinical outcomes in patients with versus without diabetes. This study employs a retrospective cohort design. Data were obtained from the Monitoring Reevaluation Platform for Key Medical Device Adverse Events-the multicenter, observational registry that includes patients undergone PCI in Beijing, Guangdong province, and Guizhou province. The primary outcome measure was the composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or any clinically indicated revascularisation procedure. Multivariable logistic regression was used to assess the association between MACE and diabetes, estimating adjusted odds ratios (ORs) and 95% confidence intervals. A total of 12,448 patients were included in the final analysis. There were 3,359 (26.98%) patients with DM and 9,089 (73.02%) without DM, respectively. The crude incidence rate of MACE was 0.92% (95% CI: 0.68-1.17%) over 12 months following PCI. Patients with diabetes had a slightly higher rate of MACEs than those without DM, but this difference did not reach statistical significance (1.01% vs. 0.88%; P&#x2009;=&#x2009;0.625). After adjustment for baseline characteristics, patients with DM were not at higher risk of MACEs than those without diabetes (OR: 1.67; 95% CI: 0.44-6.34; P&#x2009;=&#x2009;0.452). In this large, multicenter Chinese registry, DES use was associated with a low and acceptable 1-year MACE rate. Diabetes may not be an independent risk factor for adverse outcomes following DES implantation. However, given the high attrition rate in the observational registry and the potential for underestimation of events, further studies with stricter endpoint ascertainment are warranted, particularly among high-risk subgroups such as elderly patients and those with multiple comorbidities.

Chemotherapy is a common modality used for management of cancers but some agents are known to cause peripheral neuropathy. Chemotherapy induced peripheral neuropathy (CIPN) refers to a disorder in structure and functionality of peripheral sensory, motor, and autonomic neurons triggered by the toxic effects of these drugs. CIPN is a common adverse drug reaction (ADR) caused by mainly platinum analogs, vinca alkaloids and taxanes. Severe CIPN can cause paresis, complete immobilization and disability. The objectives of this study were to determine the prevalence, factors associated with and evaluate treatment of CIPN among adult patients with cancer at Mbarara Regional Cancer Centre. A cross-sectional study was conducted for a period of 2 months among adult patients with cancer receiving chemotherapy at Mbarara Regional Cancer Centre. Consecutive sampling technique was used to enroll 235 participants into the study. Data collection was done through patient interviews and file reviews. Assessment of the clinical features of CIPN was done using EORTC-QLQ-CIPN20 tool. SPSS version 27 was used for data entry and analysis. The prevalence of CIPN was 31.1%. The factors associated with occurrence of CIPN include age greater or equal to 60 years (aOR&#x2009;=&#x2009;2.04, 95% CI: 1.07-3.91, p-value&#x2009;=&#x2009;0.031), concurrent administration of non-chemotherapeutic neurotoxic drugs (aOR&#x2009;=&#x2009;6.50, 95% CI: 1.64-9.36), past resolved neuropathy prior to initiation of chemotherapy (aOR&#x2009;=&#x2009;6.99, 95% CI: 2.28-9.21). 30.1% of patients with CIPN received treatment and were managed with agents such as pregabalin, gabapentin, cachnerve, Nat B, neuroton, amitriptyline and vitamin B complex. The American Society of Clinical Oncology guideline recommends use of duloxetine for treatment of CIPN. Nearly one-third of patients at Mbarara Regional Cancer Centre had CIPN. Patient age 60 years and above, past resolved neuropathy and concurrent administration of non-chemotherapeutic neurotoxic drugs are factors associated with occurrence of CIPN. Therefore, such patients require close monitoring for the symptoms of peripheral neuropathy so that appropriate treatment can be initiated promptly.

Cryptococcosis is a severe invasive fungal infection with limited therapeutic options beyond fluconazole-based regimens. Isavuconazole, a broad-spectrum triazole antifungal, has emerged as a potential alternative, although clinical data supporting its use remain scarce. We aimed to evaluate the real-world effectiveness and safety of isavuconazole in patients with different forms of cryptococcosis. A retrospective observational study was conducted at a tertiary-care hospital, including patients with cryptococcosis who received isavuconazole at any treatment phase. Standard microbiological methods were used for pathogen identification and susceptibility testing. Demographic, clinical, and microbiological data were collected. Clinical and microbiological responses and tolerability were assessed at end of treatment or until death. Eight patients with cryptococcosis received isavuconazole, most of whom were immunocompromised. Clinical presentations included pulmonary and disseminated disease, with Cryptococcus neoformans as the predominant species. Isavuconazole was primarily used during the consolidation and maintenance phases, after induction therapy with amphotericin B and flucytosine for 2&#xa0;weeks in most cases, and as salvage therapy in two patients. It was well tolerated during prolonged treatment (6-12&#xa0;months). In the two patients with isavuconazole therapeutic drug monitoring, plasma total trough concentrations were within the therapeutic range (5 and 3.5&#xa0;&#xb5;g/mL, respectively), whereas cerebrospinal fluid total concentration levels were undetectable. A favorable clinical response was observed in four patients, while three remain on treatment with ongoing clinical improvement; one patient died early. Microbiological clearance was achieved in all culture-positive cases. Isavuconazole demonstrated clinical effectiveness in this cohort of patients across different presentations of cryptococcosis. Treatment was safe and well tolerated, supporting its role as an alternative antifungal option against Cryptococcus, particularly when fluconazole is limited by adverse effects or drug-drug interactions. However, data on central nervous system penetration were limited, and further studies are needed to better define its role in cryptococcal meningitis management.

Psychiatric randomised controlled trials increasingly privilege psychometric rating scales, yet bedside clinical training, remains the clinician's primary integrator of meaning, context, and change. Recent reconceptualisations describe clinical judgment as a three-stage process encompassing data collection through clinical interviewing, interpretationviaclinical reasoning, and decision making (Fava and Guidi, 2026; Fava et al., 2026). We provide a historically informed, conceptually focused analysis of the transition from narrative clinical impression to operationalised criteria and multi-item scales, and examine the emergence of clinician-judgment outcomes, particularly the Clinical Global Impressions (CGI) scales, as a hybrid bridge between these traditions. We argue that modern outcome assessment comprises two dominant families: multi-item symptom scales (e.g., PANSS, MADRS, HAM-A) and global clinician-judgment scales (CGI-Severity, CGI-Improvement). Global ratings can capture clinically salient information not fully represented by item totals, but only if their use preserves independent judgment. We propose "CGI 2.0": minimum standards for rater qualification, construct-focused training, structured justification, calibration/monitoring, and prespecified concordance/discordance analyses with primary symptom-scale endpoints, while cautioning against "industrialised" practices such as deriving CGI scores from multi-item totals. A clinimetric integration of psychometric methods that re-legitimises calibrated clinical judgment alongside rigorous measurement could improve interpretability, clinical relevance, and signal detection in psychopharmacology trials.

Quantitative microsampling is increasingly used in bioanalysis; however, for plasma-referenced analytes, whole-blood microsampling may introduce matrix-dependent bias related to hematocrit (HCT) and blood-to-plasma analyte distribution. This study developed and validated a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method incorporating miniaturized micro-QuEChERS extraction for the simultaneous quantification of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) in plasma, quantitative dried plasma spots (qDPS; Capitainer SEP10&#xae;), and quantitative dried blood spots (qDBS; Capitainer B&#xae;). Method validation, performed according to International Council for Harmonization (ICH) M10 and International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) recommendations, demonstrated satisfactory selectivity, linearity, accuracy, precision, recovery, matrix-effect performance, stability, and incurred sample reanalysis across all matrices. In paired samples from pediatric kidney transplant recipients (n&#xa0;=&#xa0;50), Passing-Bablok regression and Bland-Altman analysis showed close agreement between qDPS and conventional plasma, with low systematic deviation. For MPA, a small statistically significant proportional bias was observed, although most results remained within predefined clinical acceptance limits. In contrast, qDBS showed marked proportional bias and systematic underestimation compared with plasma. HCT- and regression-based correction strategies improved qDBS agreement but did not fully eliminate matrix-related discrepancies and require further external validation. These findings demonstrate that plasma-first microfluidic microsampling improves comparability with conventional plasma for MPA and MPAG by controlling matrix composition at the sampling stage. The proposed qDPS-based LC-MS/MS workflow provides a low-volume, matrix-aligned approach for plasma-referenced therapeutic drug monitoring and may support decentralized sampling in pediatric transplant recipients.

Baloxavir Marboxil, a first-in-class cap-dependent endonuclease inhibitor, is a prodrug used in influenza therapy. Reliable analytical methods are essential for its quantification in pharmaceutical formulations and biological matrices to support drug development, quality control, and pharmacokinetic studies. This review evaluates current analytical approaches, and future directions. A systematic literature search identified relevant analytical studies, which were critically compared based on principles, validation performance, and applicability. UHPLC-MS/MS is considered the gold standard, offering high sensitivity (LLOQ as low as 0.1 ng/mL), strong selectivity, and simultaneous determination of baloxavir marboxil and its active metabolite. Sample preparation techniques, particularly protein precipitation and liquid-liquid extraction, significantly influence method performance, while isotopically labeled internal standards effectively minimize matrix effects. The compound shows pronounced instability under alkaline conditions, whereas oxidative, thermal, and photolytic degradation are relatively limited. Emerging spectrofluorimetric methods provide greener alternatives but with reduced sensitivity and limited bioanalytical applicability. This review compares major analytical platforms, highlights regulatory validation requirements, and discusses clinical applications including therapeutic drug monitoring. It underscores the need for standardized, high-throughput, and sustainable analytical methods to support future research and clinical implementation.

Brain-on-a-chip is a microphysiologic platform that comprises cultured brain cells to understand brain disease pathogenesis and treatment. The blood-brain barrier (BBB) of the neurovascular unit serves as a highly selective molecular transport interface for brain homeostasis. BBB dysfunction promotes neuroinflammation, exacerbates disease progression, and contributes to neurodegenerative diseases. However, the mechanisms of BBB disruption underlying brain disorders remain poorly understood; thus, developing neurotherapeutics that can effectively cross the BBB remains a major challenge. Recent advances in microfluidic brain-on-a-chip platforms now enable the creation of BBB-on-a-chip systems that replicate key structural and functional aspects of the human BBB under dynamic flow conditions. Integration of microelectrode arrays into these microfluidic systems enhances their utility by enabling high-throughput drug screening and targeted delivery, allowing real-time monitoring of neuronal activity and network behavior. Although current brain organoid, brain-on-a-chip, and BBB-on-a-chip platforms remain in developmental stages, significant progress has been made using induced pluripotent stem cell-derived neurons, astrocytes, endothelial cells, pericytes, and microglia from healthy individuals and patients with neurodegenerative diseases. This review highlights recent advances in brain- and BBB-on-a-chip technologies and their potential applications in studying disease pathogenesis and preclinical drug screening for neurodegenerative disorders.

IntroductionThere is a lack of data supporting rationale drug use with extracorporeal membrane oxygenation (ECMO). The aim of this study was to externally validate a previously developed population pharmacokinetic model of meropenem in neonatal ECMO and continuous renal replacement therapy.MethodsA total of twenty-eight neonates with a body weight of 3.81 (3.45-4.11) kg, median (interquartile) and a postnatal age of 3 (2-4) days were enrolled. One hundred plasma concentrations of meropenem were used for external validation by a published population pharmacokinetic analysis model using NONMEM V7.3.0 (ICON Development Solutions, Ellicott City, MD, USA) and PsN v3.4.2, both running in Pirana 2.9.0. Prediction error analyses, and NPDE diagnostics were performed to assess the model's extrapolative capability. Bayesian forecasting was conducted to determine the impact of prior concentration information on predictive performance.ResultsPopulation-based predictions showed minimal overall bias but limited accuracy, with substantial variability between predicted and observed concentrations and less than half of predictions falling within an acceptable deviation range. After incorporating one prior measured concentration through Bayesian forecasting, predictive performance improved markedly. Most predictions were then close to the values observed, and overall accuracy increased substantially.ConclusionsThe meropenem population pharmacokinetic model provides unbiased but imprecise population-level predictions and is therefore not suitable for a priori dosing in neonatal ECMO patients. Including just one prior concentration greatly improves prediction, supporting the use of this model for Bayesian, therapeutic drug monitoring-guided dosing of meropenem in this vulnerable population. (The study identification number is K 2026-0116).