British Journal of Clinical Pharmacology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 30, 2024
Язык: Английский
Molecules, Год журнала: 2024, Номер 29(24), С. 5934 - 5934
Опубликована: Дек. 16, 2024
Targeted metabolomics and lipidomics are increasingly utilized in clinical research, providing quantitative comprehensive assessments of metabolic profiles that underlie physiological pathological mechanisms. These approaches enable the identification critical metabolites alterations essential for accurate diagnosis precision treatment. Mass spectrometry, combination with various separation techniques, offers a highly sensitive specific platform implementing targeted settings. Nevertheless, challenges persist areas such as sample collection, quantification, quality control, data interpretation. This review summarizes recent advances lipidomics, emphasizing their applications research. Advancements, including microsampling, dynamic multiple reaction monitoring, integration ion mobility mass highlighted. Additionally, discusses importance standardization harmonization successful implementation.
Язык: Английский
Процитировано
4
Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Rising numbers of individuals receiving psoriasis biologics achieve clear/nearly clear skin (disease control). Trial data indicate some maintain control with lower doses, especially those higher serum drug concentrations. This indicates potential for Model-Informed Precision Dosing (MIPD), an advanced therapeutic monitoring technique, in guiding dose minimisation. We developed, validated, and user-tested a precision dosing dashboard. applied MIPD approach leveraging Bayesian estimation to predict individual pharmacokinetic (PK) parameters personalised recommendations. A PK model the exemplar biologic risankizumab, derived from phase I-III trial (13123 observations/1899 patients), was externally validated using real-world UK data. The (posterior prediction: mean absolute error 0.89 mg/L; percentage 19.55%; root square 1.24 R2 0.86) had superior predictive power basic (prior prediction). incorporated into interactive dashboard, enabling input patient (serum concentrations, covariates). healthcare professionals rated dashboard user-friendly acceptable. Mean time generate interval 2 minutes. Our has incorporate other extend across disease contexts (non-response, inflammatory diseases) optimal impact on health cost outcomes.
Язык: Английский
Процитировано
0
CPT Pharmacometrics & Systems Pharmacology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 18, 2025
ABSTRACT Physiologically based pharmacokinetic (PBPK) modeling, a cornerstone of model‐informed drug development and precision dosing, simulates disposition in the human body by integrating physiological, biochemical, physicochemical parameters. While PBPK modeling has advanced globally since 1970s, China's adoption this technology followed distinctive path, characterized accelerated growth over past 2 decades. This review provides comprehensive analysis contributions to addressing knowledge gaps publication trends, application domains, platform preferences. A systematic literature search yielded 266 original research articles from PubMed up August 08, 2024. The revealed that drug–drug interaction studies constitute largest proportion analyses China. Chinese universities hospitals emerge as leading contributors among institutions Although established commercial such GastroPlus Simcyp remain popular within pharmaceutical industry, open‐source platforms like PK‐Sim are gaining significant traction applications across underscores transformative potential China, offering valuable insights into future directions challenges field.
Язык: Английский
Процитировано
0
Pathology - Research and Practice, Год журнала: 2025, Номер 269, С. 155864 - 155864
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Therapeutic Drug Monitoring, Год журнала: 2025, Номер unknown
Опубликована: Апрель 3, 2025
Background: Population pharmacokinetic (popPK) models are essential tools for optimizing ustekinumab (UST) dosing the treatment of inflammatory bowel disease (IBD) through therapeutic drug monitoring. The external validation these is necessary to ensure their predictive performance and clinical utility. aim study was externally validate 4 published popPK UST in a real-world cohort patients with IBD using prediction-based simulation-based diagnostics, as well Bayesian forecasting. Methods: Four UST, identified systematic literature review, were evaluated data from 99 374 serum concentrations. Predictive forecasting assessed statistical metrics, including mean prediction error, median error (MDPE), absolute (MADPE). acceptability criteria (MDPE ±20%, MADPE ≤30%, F20 ≥35%, F30 ≥50%) applied. Results: None satisfied predefined criteria. Xu et al model demonstrated best performance, achieving an MDPE 19.55% lowest RMSPE (2.88 mcg/mL), but (20.1%) (32.4%) values fell below thresholds. proposed by Adedokun showed strong results only 5.6% observed concentrations outside interval. Conclusions: developed exhibited most promising potential applicability model-informed precision dosing. Refinements further research required enhance use personalized therapies IBD.
Язык: Английский
Процитировано
0
Clinical Pharmacokinetics, Год журнала: 2025, Номер unknown
Опубликована: Апрель 22, 2025
Pazopanib is approved for metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma (STS) in a dose of 800 mg once daily (QD) taken under fasted conditions. In clinical practice, approximately 60% patients require reductions due to toxicity, with severe liver toxicity necessitating treatment interruptions over 10% cases. While trough concentration (Cmin,ss) target ≥ 20.5 mg/L has been established mRCC efficacy, no specific threshold exists toxicity. The objectives this study were develop population pharmacokinetic (POPPK), an exposure-liver exposure-tumor size dynamics model optimize pazopanib initial real-world patients. total, 135 included treated median starting (interquartile range, IQR: 600-800 mg) QD follow-up 120 (IQR 63-372) days. A was developed using 460 measurements from Exposure-liver evaluated time-to-event modeling, tumor growth modelling. model, 27 cases grade 2 out (20%), identified Cmin,ss > 34 associated 3.35-fold increased risk (P < 0.01). Model simulations showed that 600 significantly reduced 0.001) while maintaining 76% the simulated individuals. Tumor analyzed baseline posttreatment 111 introduction primary resistance by mixture improved fit significantly. decay rates differed between STS but exposure dependency across studied suggesting maximal inhibition at current levels. These findings suggest fasted, followed model-informed precision dosing maintain 20 mg/L, may improve efficacy-toxicity balance mitigate interruptions.
Язык: Английский
Процитировано
0
Journal of Investigative Dermatology, Год журнала: 2025, Номер unknown
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Pharmaceutics, Год журнала: 2024, Номер 16(10), С. 1295 - 1295
Опубликована: Окт. 4, 2024
Background/Objectives: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, extent individual experimental data gathered during MIPD significantly influences uncertainty in estimating PK/PD parameters, affecting clinical dose selection decisions. Methods: This study proposes a methodology to individualize ustekinumab (UTK) for 23 Spanish patients with moderate severe chronic plaque psoriasis., considering parameters within model. Results: An indirect response model from previous research was used describe relationship between UTK serum concentrations and Psoriasis Area Severity Index (PASI) score. A maximum inhibition drug effect (Imax) selected, first-order remission constant rate psoriatic skin lesion (kout = 0.016 d−1) estimated. Conclusions: The approach predicted that 35% 26% would need an optimized intensified dosage regimen, respectively, compared regimen typically practice. analysis demonstrated its utility tool selecting personalized regimens practice order optimize probability achieving targeted outcomes
Язык: Английский
Процитировано
2
Trends in Pharmacological Sciences, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
0
Pharmaceutics, Год журнала: 2024, Номер 16(12), С. 1577 - 1577
Опубликована: Дек. 10, 2024
This study evaluated the long-term effectiveness and safety of a multidisciplinary early proactive therapeutic drug monitoring (TDM) program combined with Bayesian forecasting for infliximab (IFX) dose adjustment in real-world dataset paediatric patients inflammatory bowel disease (IBD). A descriptive, ambispective, single-centre IBD who underwent IFX serum concentration measurements between September 2015 2023. The received reactive TDM before 2019 (n = 17) thereafter 21). We analysed clinical, biological, endoscopic remission; treatment failure; hospitalisations; emergency visits; adverse reactions. doses were adjusted to maintain trough concentrations ≥ 5 µg/mL, specific targets TDM. Of 38 patients, 21 had Crohn's (CD), 16 ulcerative colitis (UC), 1 undetermined IBD. mean (standard deviation) 6.83 (5.66) µg/mL (reactive) 12.38 (9.24) (proactive) ( Proactive showed no significant differences outcomes compared However, results both groups not worse than those reported other studies. Further studies larger samples are needed optimize strategies pediatric patients.
Язык: Английский
Процитировано
0