European Journal of Drug Metabolism and Pharmacokinetics最新文献

{"title":"Factors Affecting Pharmacokinetics of Sunitinib and Its Metabolite, SU12662: A Systematic Review of Population Pharmacokinetic Studies.","authors":"Heta N Shah, Jayashree Veerabhadrappa, Anagha Damre, Sharath Kumar, Vikram Gota, Surulivelrajan Mallayasamy","doi":"10.1007/s13318-025-00966-z","DOIUrl":"https://doi.org/10.1007/s13318-025-00966-z","url":null,"abstract":"<p><strong>Background and objective: </strong>Sunitinib malate is used to treat advanced renal cell carcinoma, gastrointestinal stromal, and pancreatic tumors. Wide variability in drug exposure is reported for both sunitinib and its active metabolite (SU12662). This review aimed to summarize reported population pharmacokinetics studies of sunitinib and to identify the factors affecting the pharmacokinetics of sunitinib and SU12662.</p><p><strong>Methods: </strong>A systematic search was undertaken using Scopus, Web of Science, and PubMed databases following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were included in the review if population pharmacokinetic modeling approach was used for sunitinib and/or SU12662 in adult and/or pediatric population. Data quality was assessed using the percent compliance rate of each study.</p><p><strong>Results: </strong>A total of 1820 articles were retrieved, and subsequently, 14 studies that met the inclusion criteria were included in the systematic review. Most of the studies reported two-compartment model with first-order absorption and elimination to describe sunitinib and SU12662. Body surface area, age, sex, ethnicity, tumor type, and ABCB1 and ABCG2 genotype were the significant covariates that affected the pharmacokinetics of sunitinib and SU12662.</p><p><strong>Conclusions: </strong>According to the published data from the reported studies, various covariates alter sunitinib and SU12662 exposure and thus have the potential to influence the clinical outcome of sunitinib treatment. Predictive performance assessment of these published models should be performed before implementing these models during the routine clinical practice. The summarized significant covariates affecting pharmacokinetics (PK) of sunitinib and SU12662 will facilitate model-informed precision dosing of sunitinib therapy in a clinical setting.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Implications of Pathophysiological Changes in Cachexia Syndrome: A Scoping Review.","authors":"Safeer Khan, Muhammad Nasir Kalam, Maryam Khalid, Malik Hassan Mehmood, Usman Rashid Malik, Syed Muhammad Ali","doi":"10.1007/s13318-025-00967-y","DOIUrl":"https://doi.org/10.1007/s13318-025-00967-y","url":null,"abstract":"<p><strong>Introduction: </strong>Cachexia is a complex multi-organ syndrome characterized by systemic alterations that could impact drug pharmacokinetics. This scoping review aims to examine and synthesize existing research on the pathophysiological changes in cachexia that may influence drug pharmacokinetics.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted across five databases from inception to December 2024. Study selection was refined using the population, concept, and context (PCC) framework. The population included humans and animals with cachexia, the concept focused on cachexia-induced pathophysiological changes in relation to drug pharmacokinetics, and the context encompassed any clinical, healthcare setting, or laboratory settings.</p><p><strong>Results: </strong>Out of 2684 identified studies, 53 met the inclusion criteria: 25 were based on human data, 18 on animal data, and 10 were reviews. The findings suggest that cachexia may impair drug absorption due to reduced skinfold thickness, gut dysbiosis, and structural and functional alterations in the gastrointestinal (GI) tract. Similarly, drug distribution may also be affected by changes in body composition and decreased serum albumin levels.</p><p><strong>Conclusions: </strong>Pathophysiological changes in cachexia may lead to alterations in drug absorption and distribution, contributing to variability in drug bioavailability. However, the lack of controlled clinical trials directly linking cachexia-induced physiological changes to specific drug pharmacokinetics renders these findings tentative.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Remimazolam.","authors":"Derek E Murrell, Sam Harirforoosh","doi":"10.1007/s13318-025-00963-2","DOIUrl":"https://doi.org/10.1007/s13318-025-00963-2","url":null,"abstract":"<p><p>Remimazolam, an ultrashort-acting benzodiazepine, has emerged as a promising sedative agent for procedural sedation and general anesthesia. It combines the favorable properties of traditional benzodiazepines with a rapid onset and offset of action, largely due to its unique metabolism via hepatic carboxylesterases rather than cytochrome P450 enzymes. This metabolism allows for predictable pharmacokinetics, reducing the risk of prolonged sedation and drug accumulation, particularly in patients with hepatic or renal impairment. Clinically, remimazolam demonstrates non-inferiority to midazolam and propofol, with advantages including a lower incidence of hypotension and respiratory depression. Multiple randomized controlled trials have shown its efficacy in various procedural settings, including endoscopy and bronchoscopy, with high procedural success rates and faster recovery times compared to midazolam. Additionally, remimazolam is reversible with flumazenil, further enhancing its safety profile. Pharmacokinetic studies indicate a rapid distribution phase, a short terminal half-life of approximately 37-53 min, and a clearance rate significantly higher than midazolam. Pharmacodynamic analyses confirm dose-dependent sedation effects, making remimazolam suitable for tailored sedation levels across patient populations. Special population studies suggest minimal impact of age, renal function, or mild-to-moderate hepatic impairment on drug disposition. However, rare cases of anaphylaxis and re-sedation following flumazenil administration have been reported. Given its rapid onset, predictable clearance, and favorable safety profile, remimazolam represents a valuable alternative to existing sedatives in procedural and anesthetic applications. Further research is warranted to explore its long-term safety, expanded clinical applications, and potential role in high-risk populations.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of an HPLC-MS/MS Method for Quantitative Bioanalysis of Lidocaine and its Metabolites in Human Plasma: Application in a Population Pharmacokinetic Study.","authors":"Keng Wah Foong, Didi Erwandi Mohamad Haron, Sook Hui Chaw, Yoke Lin Lo, Noridayu Omer, Pui San Loh","doi":"10.1007/s13318-025-00964-1","DOIUrl":"https://doi.org/10.1007/s13318-025-00964-1","url":null,"abstract":"<p><strong>Background and objective: </strong>Lidocaine is increasingly used perioperatively as a systemic analgesic. Quantification of lidocaine and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), is essential for understanding its pharmacokinetics and pharmacodynamics. Existing methods have limitations in throughput, concentration ranges, or do not simultaneously measure lidocaine and metabolites. This study aims to develop and validate a simple, rapid, and robust high-performance liquid chromatography-mass spectrometry (HPLC-MS)/MS method for their simultaneous quantification in plasma from surgical patients receiving intravenous lidocaine.</p><p><strong>Methods: </strong>Analytes were extracted from 75 µL of plasma by protein precipitation with 300 µL of methanol containing lidocaine-d10 (internal standard). After centrifugation for 5 minutes and filtration, 5 µL was injected onto a Phenomenex Luna C8(2) column (100 × 2.0 mm, 5 µm), achieving chromatographic separation within 5 minutes by gradient elution with 0.01% formic acid in water (mobile phase A) and acetonitrile-methanol 50:50 (mobile phase B). Mass spectrometry detection employed positive electrospray ionization with multiple reaction monitoring. The method uses a widely accessible HPLC-MS/MS platform, requires low plasma volume, and features streamlined sample preparation.</p><p><strong>Results: </strong>This method demonstrated good selectivity and specificity, minimal carryover, and reproducible recovery and matrix effects. Calibration curves were linear over 0.01-5 mg/L for lidocaine and 0.01-1.5 mg/L for MEGX and GX. Within-day and between-day accuracy and precision met acceptance criteria, and analytes remained stable under relevant conditions.</p><p><strong>Conclusions: </strong>This validated assay requires low plasma volume and minimal preparation for simultaneous quantification of lidocaine and metabolites. It was successfully applied in a population pharmacokinetic study of surgical patients receiving intravenous lidocaine, supporting optimized dosing strategies.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulated Dosing Regimens of Subcutaneous Infliximab in Adults and Children with Inflammatory Bowel Disease: Exploring Switch and Initiation Strategies.","authors":"Rianne A Weersink, Ron J Keizer, Luc J J Derijks","doi":"10.1007/s13318-025-00959-y","DOIUrl":"10.1007/s13318-025-00959-y","url":null,"abstract":"<p><strong>Introduction: </strong>An increasing number of patients in clinical practice are transitioning from intravenous (IV) to subcutaneous (SC) dosing of infliximab. In this simulation study, we evaluated hypothetical dosing scenarios both for typical adults and adults with obesity and for children switching from steady-state IV to SC infliximab, as well as those initiating SC infliximab therapy.</p><p><strong>Methods: </strong>By combining two previous published infliximab models, we were able to simulate both IV and SC dosing in adults and children. Various dosing regimens were simulated using a large virtual population. In each scenario, the distribution of trough concentrations and area under the plasma concentration-time curve (AUC) was calculated.</p><p><strong>Results: </strong>Peak levels were higher after IV dosing compared with SC dosing, while trough levels were higher after SC dosing, leading to more stable infliximab levels over time. Overall exposure remained largely similar when switching from a standard IV to SC dosing regimen. Patients with a high body mass index and those on high-frequency IV dosing regimens of infliximab demonstrated reduced exposure when transitioned to the fixed SC dose. Paediatric patients exhibited higher exposure on the fixed SC dose. Simulation of SC induction schemes demonstrated early achievement of steady-state plasma levels.</p><p><strong>Conclusion: </strong>Infliximab exposure (AUC) remains largely similar when transitioning from standard IV to SC dosing. Current dosing regimens may not be optimal for patients with severe obesity, paediatric patients and patients on high-frequency infliximab regimens. These findings provide a foundation for future clinical research to refine SC infliximab dosing in these populations.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":"419-430"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tacrolimus Trough Concentrations are Not Impacted by Epstein-Barr Virus Serology and Viral Load in Pediatric Liver Transplant Recipients.","authors":"Amber M Te Lintelo, Lisa F van Wier, Hubert P J van der Doef, Jos G W Kosterink, René Scheenstra, Coretta C van Leer, Arno R Bourgonje, Daan J Touw, Paola Mian","doi":"10.1007/s13318-025-00954-3","DOIUrl":"10.1007/s13318-025-00954-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>Epstein-Barr virus (EBV) is a common herpesvirus among pediatric liver transplant recipients, but it can have serious complications, such as post-transplant lymphoproliferative disease. EBV is hypothesized to influence tacrolimus concentrations by increasing inflammatory cytokines that regulate the expression of cytochrome-P-450 enzymes involved in tacrolimus pharmacokinetics. This study aims to examine the association between EBV serostatus and viral load, and tacrolimus trough concentrations corrected for the dose and recipient weight [weight-adjusted concentration-to-dose (C/D) ratios].</p><p><strong>Materials and methods: </strong>This retrospective study includes pediatric liver transplant recipients aged 0-18 years old, transplanted at the University Medical Center Groningen between January 2008 and September 2021. This study utilized two cohorts: a cross-sectional and a longitudinal study database.</p><p><strong>Results: </strong>The association between EBV serostatus and the tacrolimus pharmacokinetics was examined using 45 recipients from both cohorts. The effect of EBV viral load on tacrolimus pharmacokinetics was examined using the longitudinal study database, which included 25 EBV-positive recipients. No significant effect of EBV on the tacrolimus weight-adjusted C/D ratios was found, for either EBV serostatus (p = 0.85) or EBV viral load (p = 0.85).</p><p><strong>Conclusions: </strong>This study suggests that the standard protocol of tacrolimus dosing does not seem to require adjustments due to changes in EBV serostatus or viral load.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":"371-381"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioequivalence and Pharmacokinetic Evaluation of Two Metformin Hydrochloride Tablets Under Fasting and Fed Conditions in Healthy Chinese Volunteers.","authors":"Yuxing Huang, Qiuhan Cai, Meifang Li, Shengxuan Guo, Gaiying Dong, Siyuan Hu, Chengliang Zhong","doi":"10.1007/s13318-025-00961-4","DOIUrl":"10.1007/s13318-025-00961-4","url":null,"abstract":"<p><strong>Background and objectives: </strong>With diabetes prevalence rising and original formulations unable to meet demand, establishing generic equivalence is crucial for treatment accessibility. This study evaluated the bioequivalence of generic metformin hydrochloride (0.25 g) versus the reference drug in Chinese volunteers under fasting and fed conditions.</p><p><strong>Methods: </strong>In this randomized, open-label, two-period crossover trial, 26 healthy volunteers per group received single doses under fasting and fed conditions. Plasma concentrations were measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, pharmacokinetic metrics were calculated using the WinNonlin 6.3 software, and bioequivalence was evaluated using SAS 9.4.</p><p><strong>Results: </strong>Under fasting conditions, the geometric mean ratios (GMRs) between the test and reference groups were 103.12% (C_max), 103.65% (AUC_0-t), and 103.31% (AUC_0-∞), with 90% CIs of 92.64-114.78%, 96.04-111.85%, and 96.00-111.17%, respectively. Fed conditions yielded GMRs of 93.98% (C_max), 97.34% (AUC_0-t), and 96.97% (AUC_0-∞), with 90% CIs of 89.42-98.78%, 92.72-102.18%, and 92.40-101.78%, respectively. All these parameters met bioequivalence criteria (80-125%). Median T_max was delayed under fed conditions (2.125 h vs. 4.000 h), with consistent food effects (reduced C_max and AUC) and safety profiles between formulations.</p><p><strong>Conclusion: </strong>These results demonstrate that the generic metformin formulation is bioequivalent to the innovative product and well tolerated in Chinese healthy volunteers under both fasting and fed conditions.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":"50 5","pages":"431-440"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of CYP3A5, ABCB1, and CYP2C8 Polymorphisms with Renal Function in Kidney Transplant Recipients Receiving Tacrolimus.","authors":"Zühal Kaltuş, Nuşin Harmancı, Garip Şahin, Engin Yıldırım","doi":"10.1007/s13318-025-00955-2","DOIUrl":"10.1007/s13318-025-00955-2","url":null,"abstract":"<p><strong>Background/objectives: </strong>Tacrolimus (TAC, FK-506) is a calcineurin inhibitor commonly used to prevent organ rejection in transplant patients. It has a narrow therapeutic index and nephrotoxic effects, characterized by interindividual dose variability. TAC is metabolized by the CYP450 (CYP3A5, CYP3A4) enzyme system and transported by P-glycoprotein (ABCB1). Additionally, the CYP2C8 enzyme has been suggested to play a protective role against both graft rejection and drug-induced toxicity. Genetic polymorphisms in these pathways may influence the risk of tacrolimus-related nephrotoxicity. This retrospective cohort study was conducted to evaluate the association between CYP3A5, ABCB1, and CYP2C8 gene polymorphisms and renal function in kidney transplant recipients METHODS: This study investigated the impact of CYP3A5, ABCB1 and CYP2C8 polymorphisms on blood TAC level and kidney function in renal transplant patients. Genotyping was conducted to determine allele frequencies for CYP3A5 (6986A>G), ABCB1 (13435C>T), and CYP2C8 (A1196G) polymorphisms. Renal function was assessed by measuring serum creatinine, estimated glomerular filtration rate (eGFR), and protein/creatinine ratios at 3, 6, and 12 months post-transplantation.</p><p><strong>Result: </strong>At 12 months post-transplant, the median serum creatinine level was significantly higher in patients with CYP2C8 (*1/*3 and *3/*3) genotypes compared to those with the CYP2C8*1/*1 genotype (p = 0.021). Additionally, the increase in creatinine from the 3rd to the 12th month was significantly greater in the CYP2C8 (*1/*3 and *3/*3) group (p = 0.036). No significant differences were observed in TAC dosage, blood concentration, or renal function between ABCB1 genotype groups. Although daily TAC doses differed significantly between CYP3A5 genotypes, renal function did not significantly vary.</p><p><strong>Conclusion: </strong>In light of these data, CYP2C8 gene polymorphism has been associated with an increase in serum creatinine, one of the key markers of renal function. ABCB1 gene polymorphism showed no association while CYP3A5 gene polymorphism influenced TAC dose; however, further studies with larger cohorts are required to clarify these associations.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":"383-397"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the Role of Plasma-to-Blood Partitioning in Pharmacokinetics.","authors":"Amarinder Singh, Bernd Meibohm","doi":"10.1007/s13318-025-00958-z","DOIUrl":"10.1007/s13318-025-00958-z","url":null,"abstract":"","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":"447-448"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Effect of Ticagrelor Dose Interruption and Treatment Resumption with or without Bolus Doses Through Population PK/PD Simulation.","authors":"Hiroyoshi Matsui, Le Thien Truc Pham, Eyob Adane","doi":"10.1007/s13318-025-00957-0","DOIUrl":"10.1007/s13318-025-00957-0","url":null,"abstract":"<p><strong>Background: </strong>Ticagrelor is an oral P2Y₁₂ receptor antagonist used mostly in combination with aspirin, in patients with acute coronary syndromes (ACS). Ticagrelor is discontinued 3-5 days before major procedures. Due to its reversible effect, discontinuation is likely to increase the risk of thrombosis. While the effect of dose interruptions on the risk of thrombosis has not been directly studied, pharmacokinetic/pharmacodynamic (PK/PD) simulations provide useful insights.</p><p><strong>Objectives: </strong>The objective of the current study was to simulate the impact of therapy interruption on the PK/PD of ticagrelor.</p><p><strong>Methods: </strong>The oral absorption of ticagrelor was described by a transit compartment model, and population PK/PD parameters were obtained from published literature. The PD of ticagrelor was described using a sigmoidal direct-response I_max model. A population PK/PD model describing the relationship between ticagrelor dose, plasma concentrations, and P2Y₁₂ reaction units (PRU) was used to perform simulations using Simulx (Lixoft, France). Simulated patients (n = 1000) received a loading dose of 180 mg followed by a maintenance dose of 90 mg twice daily orally for 15-days. Doses were stopped on day 8 for 0-5 days and resumed with or without a loading dose.</p><p><strong>Results: </strong>During uninterrupted ticagrelor use, median PRUs ranged between ~ 13 to ~ 40, with > 70% below low platelet reactivity (LPR). The % of PRUs below high platelet reactivity (HPR) drops to ~ 47%, ~ 11%, ~ 2% and 0% upon dose interruption of 1, 2, 3, and 5 days, respectively. Within 2 h of dose resumption with either the loading or the maintenance dose, > 94% of PRUs were below LPR.</p><p><strong>Conclusion: </strong>Our results suggest the need for individualizing duration of dose interruption prior to surgery and its resumption afterwards.</p>","PeriodicalId":11939,"journal":{"name":"European Journal of Drug Metabolism and Pharmacokinetics","volume":" ","pages":"409-418"},"PeriodicalIF":2.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}