European Journal of Clinical Pharmacology最新文献

{"title":"The impact of age and renal function on the pharmacokinetics and protein binding characteristics of fludarabine in paediatric and adult patients undergoing allogeneic haematopoietic stem cell transplantation conditioning.","authors":"Christa E Nath, Sebastian P A Rosser, Kiran K Nath, Jason Chung, Stephen Larsen, John Gibson, Melissa Gabriel, Peter J Shaw, Steven J Keogh","doi":"10.1007/s00228-024-03751-0","DOIUrl":"10.1007/s00228-024-03751-0","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the population pharmacokinetics of unbound F-Ara-A (the circulating metabolite of fludarabine) in 211 patients (age range, 0.1-63.4 years) undergoing allogeneic haematopoietic stem cell transplantation conditioning.</p><p><strong>Methods: </strong>Total (n = 2480) and unbound (n = 1403) F-Ara-A concentrations were measured in blood samples collected at timed intervals after fludarabine doses ranging from 10 to 50 mg/m² and infused over 0.42-1.5 h. A three-compartment population pharmacokinetic model was developed based on unbound plasma concentrations and used to estimate F-Ara-A unbound pharmacokinetic parameters and fraction unbound (fu). A number of covariates, including glomerular filtration rate (GFR) and post-menstrual age (PMA), were evaluated for inclusion in the model.</p><p><strong>Results: </strong>The base population mean estimates ± relative standard error (%RSE) for unbound clearance from the central compartment (CLu) and inter-compartmental clearances (Q2u, Q3u) were 3.42 ± 3%, 6.54 ± 24% and 1.47 ± 16% L/h/70 kg, respectively. The population mean estimates (%RSE) for the unbound volume of distribution into the central (V1u) and peripheral compartments (V2u, V3u) were 9.65 ± 8%, 8.17 ± 9% and 16.4 ± 10% L/70 kg, respectively, and that for fu was 0.877 ± 1%. Covariate model development involved differentiating F-Ara-A CLu into non-renal (1.81 ± 9% L/h/70 kg) and renal components (1.02 ± 9%*GFR L/h/70 kg). A sigmoidal maturation factor was applied to renal CLu, with population mean estimates for the Hill exponent and PMA at 50% mature of 2.97 ± 4% and 69.1 ± 8% weeks, respectively.</p><p><strong>Conclusion: </strong>Patient age and GFR are predictors of unbound F-Ara-A CLu. This has the potential to impact dose requirements. Dose individualisation by target concentration intervention will be facilitated by this model once it is externally validated.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1967-1987"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serious gaming as potential training tool for recognition of adverse drug reactions: side-effect exposure-medical education (SeeMe).","authors":"Ingmar Bergs, Laura Bell, Sebastian Fedrowitz, Tim Krüger, Martin Lemos, Julia C Stingl, Katja S Just","doi":"10.1007/s00228-024-03739-w","DOIUrl":"10.1007/s00228-024-03739-w","url":null,"abstract":"<p><strong>Purpose: </strong>The recognition of adverse drug reactions (ADRs) is an important part of daily clinical work. However, medical education in this field is mostly drug-based and does not address adequately the complexity of this field regarding individual risk factors and polypharmacy. This study investigates the potential of the web-based serious game SeeMe (side-effect exposure-medical education) in pharmacological education of medical students to improve the recognition of relevant ADRs.</p><p><strong>Methods: </strong>One hundred fifty-seven medical students were recruited to evaluate the serious game SeeMe. SeeMe was developed to improve knowledge and recognition of ADRs in clinical practice. Players take on the role of a physician trying to understand fictional patients with ADRs. Before and after an 8-week playing period, an evaluation was carried out through a pre- and post-questionnaire and a pre- and post- knowledge test.</p><p><strong>Results: </strong>The students achieved significantly better results in the knowledge test, as almost twice as many exam-relevant questions were answered correctly (p < 0.001). The serious game had a positive effect on the students' perception of the importance of ADRs.</p><p><strong>Conclusion: </strong>This study demonstrates the potential of web- and case-based fictional serious games in medical education. The improved recognition of side effects represents a crucial step for education and training in clinical pharmacology. Future versions of the serious game may take this further and focus on training in the treatment of ADRs and their relevance in various healthcare professions.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1787-1793"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reference guides for the safe use of drugs during pregnancy: a systematic review and comparative analysis.","authors":"Xue-Feng Jiao, Panda Qiu, Zheyun Song, Xue Peng, Hailong Li, Linan Zeng, Lingli Zhang","doi":"10.1007/s00228-024-03736-z","DOIUrl":"10.1007/s00228-024-03736-z","url":null,"abstract":"<p><strong>Purpose: </strong>To comprehensively evaluate and compare all the available reference guides for the safe use of drugs during pregnancy, with the goal of determining the scientificity and reliability of these reference guides.</p><p><strong>Methods: </strong>We searched PubMed, EMbase, CNKI, Wanfang Database, and VIP database to comprehensively identify the available reference guides. Moreover, we selected 103 drugs based on relevant literatures, and compared the recommendations of each drug from different reference guides.</p><p><strong>Results: </strong>A total of 14 available reference guides were identified. However, none of these reference guides assessed the risk of bias of original studies or the quality of current evidence. Seven reference guides adopted expert consensus method to formulate pregnancy recommendations, while the rest reference guides did not report the formation method. Moreover, 77.7% of the selected drugs had inconsistent recommendations among different reference guides. In addition, the referenced human and animal studies for the same drug differed among different reference guides.</p><p><strong>Conclusion: </strong>Our results indicate that current reference guides for the safe use of drugs during pregnancy are less scientific and reliable, and there are considerable discrepancies in recommendations from different reference guides concerning drug use during pregnancy. The reasons for the discrepancies in recommendations include ① the literature search in most reference guides was not comprehensive, ② none of the available reference guides assessed the risk of bias of original studies or the quality of current evidence, and ③ the method adopted by current reference guides to formulate recommendations had obvious subjectivity and lacked of scientificity.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1625-1657"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of isoniazid-induced psychosis: a systematic review of case reports and case series.","authors":"Keerthanaa B, Rashmi Appaji, Levin Thomas, Tejaswini Baral, Skanda N, Chaithra, Sonal Sekhar M, Kavitha Saravu, Krishna Undela, Mahadev Rao","doi":"10.1007/s00228-024-03738-x","DOIUrl":"10.1007/s00228-024-03738-x","url":null,"abstract":"<p><strong>Purpose: </strong>Isoniazid, a first-line antitubercular drug, is associated with nervous system adverse drug reactions such as seizures, peripheral neuropathy, and psychosis. This systematic review of case reports and case series aimed to characterize the demographic, social, and clinical factors associated with isoniazid-induced psychosis in patients with active tuberculosis (TB) and those who received isoniazid for latent TB infection (LTBI).</p><p><strong>Methods: </strong>We comprehensively searched the Embase, PubMed, and Scopus databases to identify relevant studies published between the date of inception of the database and June 2024.</p><p><strong>Results: </strong>A total of 28 studies, including 21 case reports and 7 case series involved 37 patients who developed isoniazid-induced psychosis. A higher frequency of isoniazid-induced psychosis was observed during the first 2 months of treatment, with a relatively early onset observed among patients aged 18 years or less. Delusions and/or hallucinations are the common symptoms of isoniazid-induced psychosis. Psychomotor disturbances, disorganized speech or formal thought disorder, disorganized or abnormal behaviour, and neuropsychiatric symptoms (sleep disturbances, hostility or aggression, confusion, affective symptoms, anxiety symptoms, and cognitive difficulties) were the other symptoms observed in the included studies. More than 80% of cases rechallenged with isoniazid resulted in the recurrence of psychotic symptoms.</p><p><strong>Conclusion: </strong>Patients with TB and LTBI should be assessed for psychotic and neuropsychiatric symptoms during isoniazid therapy, mainly in the first 2 months. Further research is required to understand the impact of underlying risk factors, such as genetic predisposition and isoniazid pharmacokinetics, as well as the clinical utility and dosage recommendations of pyridoxine for managing isoniazid-induced psychosis.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1725-1740"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of SLC6A2 and CYP2D6 polymorphisms' effects on atomoxetine treatment in attention deficit and hyperactivity disorder.","authors":"Ismail Hasan Kole, Pınar Vural, Beste Yurdacan, Adem Alemdar, Caner Mutlu","doi":"10.1007/s00228-024-03744-z","DOIUrl":"10.1007/s00228-024-03744-z","url":null,"abstract":"<p><strong>Background: </strong>There is insufficient replicated data to establish a relationship between the polymorphisms of SLC6A2 and CYP2D6 and the treatment responses of atomoxetine (ATX) in ADHD. We focused on evaluating the effect of top-line single nucleotide polymorphisms (SNPs) in SLC6A2 and CYP2D6 on the ATX treatment response in attention deficit and hyperactivity disorder (ADHD).</p><p><strong>Methods: </strong>Of 160 patient records, 34 patients who met the inclusion criteria were evaluated to determine the relationship between genotypes of ten SNPs (six of SLC6A2 and four of CYP2D6) and ATX treatment response. Additionally, the connection between SNPs of CYP2D6 and the severity of side effects associated with ATX was analyzed in 37 patients, including the 34 study patients, and three patients discontinued because of ATX-dependent side effects.</p><p><strong>Results: </strong>All six polymorphisms we studied in SLC6A2 were associated with the treatment response of ATX. Clinical improvement in oppositional defiant disorder symptoms of patients with ADHD was only observed in carriers of the homozygous \"C\" allele of rs3785143 (p_odd = 0.026). We detected an association between higher CGI-side-effect severity scores and the \"TT\" genotype of rs1065852 polymorphism in CYP2D6 (p = 0.043).</p><p><strong>Conclusions: </strong>The findings of this study suggest that genotypes of polymorphisms within the SLC6A2 and CYP2D6 may play an influential role in treatment response or the severity of side effects associated with ATX in ADHD patients.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1773-1785"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug administration via feeding tubes-a procedure that carries risks: systematic identification of critical factors based on commonly administered drugs in a cohort of stroke patients.","authors":"Jana Sommerfeldt, Hannes Sartorius, Bettina von Sarnowski, Sandra Klein, Christoph A Ritter","doi":"10.1007/s00228-024-03723-4","DOIUrl":"10.1007/s00228-024-03723-4","url":null,"abstract":"<p><strong>Purpose: </strong>Drug administration via feeding tubes is considered a process with many uncertainties. This review aimed to give a comprehensive overview of data available on feeding tube application and to carry out risk assessments for drug substances commonly administered to stroke patients.</p><p><strong>Methods: </strong>Drugs frequently administered via feeding tubes were identified through a retrospective analysis of discharge letters from a stroke unit. Physicochemical, pharmacokinetic, and stability properties of these drugs and data on drug-enteral nutrition interactions were systematically searched for in the European Pharmacopoeia, Hagers Handbook of Pharmaceutical Practice, Birchers clinical-pharmacological data compilation, and the Martindale Complete Drug Reference, as well as from databases including DrugBank, DrugDex, PubChem, Google Scholar, and PubMed.</p><p><strong>Results: </strong>Of the drugs most commonly administered via feeding tubes in the present stroke patient cohort, bisoprolol, candesartan, and ramipril could be considered the least critical due to their overall favourable properties. Acetylsalicylic acid, amlodipine, hydrochlorothiazide, omeprazole and esomeprazole, simvastatin, and torasemide pose risks based on pH or light-dependent instability or proposed food effects. The most critical drugs to be administered via feeding tubes are considered to be furosemide, levodopa, and levothyroxine as they show relevant instabilities under administration conditions and substantial food effects; the latter two even possess a narrow therapeutic index. However, little information is available on drug-tube and drug-formula interactions.</p><p><strong>Conclusion: </strong>Feeding tube administration of medications turned out to be a highly complex process with several unmet risks. Therefore, investigations that systematically assess these risk factors using clinically relevant model systems are urgently needed.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1599-1623"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of pharmacokinetic target attainment and hematological toxicity of linezolid in pediatric patients.","authors":"Manal Abouelkheir, Maram R Aldawsari, Leen Ghonem, Aliyah Almomen, Emad Alsarhani, Sarah Alsubaie, Saeed Alqahtani, Zeyad Kurdee, Abdullah Alsultan","doi":"10.1007/s00228-024-03740-3","DOIUrl":"10.1007/s00228-024-03740-3","url":null,"abstract":"<p><strong>Background: </strong>Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetic (PK) target attainment in pediatrics.</p><p><strong>Objective: </strong>To evaluate the percentage of pediatrics achieving the PK targets of linezolid with standard dosing regimens and to assess the incidence and risk factors associated with its hematologic toxicity.</p><p><strong>Methods: </strong>This prospective observational study included pediatric patients aged 0-14 who received linezolid for suspected or proven Gram-positive infections. Linezolid trough concentrations and the 24-h area under the curve (AUC₂₄) were estimated, and hematologic toxicity was assessed.</p><p><strong>Results: </strong>Seventeen pediatric patients (5 neonates and 12 older pediatrics) were included. A wide variability was observed in linezolid's trough and AUC₂₄ (ranging from 0.5 to 14.4 mg/L and from 86 to 700 mg.h/L, respectively). The median AUC₂₄ was significantly higher in neonates than older pediatrics (436 [350-574] vs. 200 [134-272] mg,h/L, P = 0.01). Out of all patients, only 41% achieved adequate drug exposure (AUC₂₄ 160-300 mg.h/L and trough 2-7 mg/L), with 24% having subtherapeutic, and 35% having higher-than-optimal exposures. Hematological toxicity was observed in 53% of cases. Identified risk factors include treatment duration over 7 days, baseline platelet counts below 150 × 10⁹/L, sepsis/septic shock, and concomitant use of meropenem.</p><p><strong>Conclusions: </strong>Linezolid's standard dosing failed to achieve its PK targets in approximately half of our pediatric cohort. Our findings highlight the complex interplay between the risk factors of linezolid-associated hematological toxicity and underscore the importance of its vigilant use and monitoring, particularly in pediatrics with concomitant multiple risk factors.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1807-1817"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voriconazole therapeutic drug monitoring including analysis of CYP2C19 phenotype in immunocompromised pediatric patients with invasive fungal infections.","authors":"Matylda Resztak, Paulina Zalewska, Jacek Wachowiak, Agnieszka Sobkowiak-Sobierajska, Franciszek K Główka","doi":"10.1007/s00228-024-03752-z","DOIUrl":"10.1007/s00228-024-03752-z","url":null,"abstract":"<p><strong>Purpose: </strong>Therapeutic drug monitoring (TDM) of voriconazole (VCZ) should be mandatory for all pediatric patients with invasive fungal infections (IFIs). The narrow therapeutic index, inter-individual variability in VCZ pharmacokinetics, and genetic polymorphisms cause achieving therapeutic concentration during therapy to be challenging in this population.</p><p><strong>Methods: </strong>The study included 44 children suffering from IFIs treated with VCZ. Trough concentrations (C_trough) of VCZ ware determined by the HPLC-FLD method. Identification of the CYP2C19*2 and CYP2C19*17 genetic polymorphisms was performed by PCR-RFLP. The correlation between polymorphisms and VCZ C_trough was analyzed. Moreover, the effect of factors such as dose, age, sex, route of administration, and drug interactions was investigated.</p><p><strong>Results: </strong>VCZ was administered orally and intravenously at a median maintenance dosage of 14.7 mg/kg/day for a median of 10 days. The VCZ C_trough was highly variable and ranged from 0.1 to 6.8 mg/L. Only 45% of children reached the therapeutic range. There was no significant association between C_trough and dosage, age, sex, route of administration, and concomitant medications. The frequencies of variant phenotype normal (NM), intermediate (IM), rapid (RM) and ultrarapid metabolizers (UM) were 41%, 18%, 28%, and 13%, respectively. C_trough of VCZ were significantly higher in NM and IM groups compared with RM, and UM groups.</p><p><strong>Conclusion: </strong>The C_trough of VCZ is characterized by inter-individual variability and a low rate of patients reaching the therapeutic range. The significant association exists in children between VCZ C_trough and CYPC19 phenotype. The combination of repeated TDM and genotyping is necessary to ensure effective treatment.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1829-1840"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients.","authors":"Astrid Heida, Nynke G L Jager, Rob E Aarnoutse, Brenda C M de Winter, Huib de Jong, Ron J Keizer, Elisabeth A M Cornelissen, Rob Ter Heine","doi":"10.1007/s00228-024-03743-0","DOIUrl":"10.1007/s00228-024-03743-0","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization.</p><p><strong>Methods: </strong>Data were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM. Subsequently, we externally evaluated the final model using data from another academic hospital. The final model was used to develop an optimized dosing regimen.</p><p><strong>Results: </strong>Thirty pediatric patients were included of whom 266 measured MPA plasma concentrations, including 20 full pharmacokinetic (PK) curves and 24 limited sampling curves, were available. A two-compartment model with a transition compartment for Erlang-type absorption best described the data. The final population PK parameter estimates were K_tr (1.48 h^-1; 95% CI, 1.15-1.84), CL/F (16.0 L h^-1; 95% CI, 10.3-20.4), V_c/F (24.9 L; 95% CI, 93.0-6.71E25), V_p/F (1590 L; 95% CI, 651-2994), and Q/F (36.2 L h^-1; 95% CI, 9.63-74.7). The performance of the PK model in the external population was adequate. An optimized initial dose scheme based on bodyweight was developed. With the licensed initial dose, 35% of patients were predicted to achieve the target AUC, compared to 42% using the optimized scheme.</p><p><strong>Conclusion: </strong>We have successfully developed a pharmacokinetic model for MPA in pediatric renal transplant patients. The optimized dosing regimen is expected to result in better target attainment early in treatment. It can be used in combination with model-informed follow-up dosing to further individualize the dose when PK samples become available.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1761-1771"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fixed parameters in the population pharmacokinetic modeling of valproic acid might not be suitable: external validation in Chinese adults with epilepsy or after neurosurgery.","authors":"Ruoyun Wu, Kai Li, Zhigang Zhao, Shenghui Mei","doi":"10.1007/s00228-024-03746-x","DOIUrl":"10.1007/s00228-024-03746-x","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to assess the predictive performance of published valproic acid (VPA) population pharmacokinetic (PPK) models using an external data set in Chinese adults with epilepsy or after neurosurgery.</p><p><strong>Methods: </strong>A total of 384 concentrations from 290 Chinese adults with epilepsy or after neurosurgery were used for external validation. Data on published VPA PPK models were extracted from the literature. Prediction-based diagnostics (such as F20 and F30), simulation-based diagnostics, and Bayesian forecasting were used to evaluate the predictability of models.</p><p><strong>Results: </strong>The results of prediction-based diagnostics of all models were unsatisfactory. Models B, F, and H showed the best prediction performance in simulation-based diagnostics and Bayesian forecasting, demonstrating superior precision and accuracy. Bayesian forecasting demonstrated significant improvements in the model predictability.</p><p><strong>Conclusion: </strong>The published PPK models showed extensive variation in predictive performance for extrapolation among Chinese adults with epilepsy or after neurosurgery patients. Fixed parameters of Vd and Ka in the PPK modeling of VPA might be the reason for the unsatisfied predictive performance. Bayesian forecasting significantly improved model predictability and may help to individualize VPA dosing.</p>","PeriodicalId":11857,"journal":{"name":"European Journal of Clinical Pharmacology","volume":" ","pages":"1819-1828"},"PeriodicalIF":2.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}