Pharmacotherapy最新文献

{"title":"Cost-Effectiveness Analysis of Patient Self-Management of Warfarin Among Patients With Non-Valvular Atrial Fibrillation.","authors":"Warittakorn Kategeaw, Daniel M Witt, Jordan B King, Daniel C Malone, Nathorn Chaiyakunapruk","doi":"10.1002/phar.70154","DOIUrl":"10.1002/phar.70154","url":null,"abstract":"<p><strong>Background: </strong>Patient self-management (PSM) is a warfarin management strategy that allows patients to independently adjust their doses. PSM significantly reduces thrombosis events and has been widely implemented internationally. However, adoption of PSM is limited in the United States. This study estimated the cost-effectiveness of PSM compared with available strategies, including anticoagulation management services (AMS) and usual care (UC) for patients with non-valvular atrial fibrillation (NVAF) aged 70 years and older in the United States.</p><p><strong>Methods: </strong>A cost-effectiveness analysis was performed to estimate lifetime costs and outcomes of PSM compared with AMS and UC employing a Markov model. The model simulated a 70-year-old with NVAF over the patient's lifetime from modified societal and payer perspectives. Transition probabilities were derived from annual event rates reported in the ARISTOTLE trial. Comparative efficacy and safety among the interventions were obtained from a network meta-analysis. Costs, presented in 2024 US dollars (USD), and utility data were obtained from data sources in the United States. A discount rate of 3% was applied for future costs and outcomes. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the findings.</p><p><strong>Results: </strong>The lifetime costs from the modified societal perspective were $137,509 USD for UC, $129,216 USD for AMS, and $76,515 USD for PSM. Discounted quality-adjusted life years (QALYs) were estimated to be 8.27 for UC, 8.30 for AMS, and 8.47 for PSM. Additionally, PSM substantially reduced stroke incidence compared with AMS and UC, contributing to lower costs and greater QALYs. Probabilistic sensitivity analysis showed that PSM appeared to be the most cost-effective at any willingness-to-pay threshold.</p><p><strong>Conclusions: </strong>PSM is the most cost-effective strategy for managing warfarin in the target population at any willingness-to-pay threshold. Implementation of PSM in the US health care setting should be considered.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 6","pages":"e70154"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147942433","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":"Pharmacokinetic Analysis of Intravenous Push Cefepime in Critically Ill Patients With Sepsis.","authors":"Susan E Smith, Rehana Bagodiya, Phuong Luong, Sakshi Shinde, Christopher M Bland, Christopher Barry, Michael G Bartlett, Nicholas R Fox, Trisha N Branan","doi":"10.1002/phar.70152","DOIUrl":"10.1002/phar.70152","url":null,"abstract":"<p><strong>Background: </strong>Intravenous push (IVP) administration of cefepime increases ease of preparation and limits the need for small volume parenterals. The data on IVP pharmacokinetic/pharmacodynamic (PK/PD) parameters are limited, but may be especially relevant in critically ill patients with altered PK/PD for time-dependent antibiotics like cefepime. The objective of this study was to characterize the PK profile and PD target attainment of IVP cefepime in critically ill patients with sepsis.</p><p><strong>Methods: </strong>In this institutional review board-approved, prospective, noninterventional PK study, hospitalized adult patients receiving IVP cefepime were included if they had a central/midline catheter, intensive care unit (ICU) length of stay ≥ 48 h, creatinine clearance > 30 mL/min without renal replacement therapy, and diagnosis of sepsis. Blood samples were obtained at cefepime steady state immediately before and at 5, 15, 30, 60, 120, and 240 min after a dose. Serum concentrations of cefepime were measured using high-performance liquid chromatography with ultraviolet detection. Patient characteristics and outcomes were collected retrospectively from the electronic health record. The primary outcome was the PK profile of cefepime following IVP administration.</p><p><strong>Results: </strong>Patients (n = 17) had a median age of 69 years, body mass index (BMI) of 29.9 kg/m², creatinine clearance of 94 mL/min, and sequential organ failure assessment (SOFA) score of 9. Following IVP administration, PK analysis demonstrated a maximum concentration (C_max) of 158 μg/mL, time to maximum concentration (T_max) of 5 min, area under the curve (AUC) of 286.95 μg × h/mL, and elimination rate constant (K_e) of 0.31 h^-1. Additionally, the analysis showed a volume of distribution of 43.91 L, elimination half-life (t_½) of 3.76 h, clearance (CL) of 7.86 L/h, and time above minimum inhibitory concentration (T > MIC) of 86%.</p><p><strong>Conclusions: </strong>Intravenous push cefepime in critically ill patients achieved systemic exposure comparable to traditional intermittent infusion but demonstrated substantial interpatient PK variability. These findings highlight the impact of critical illness on cefepime disposition and support further evaluation of personalized cefepime dosing for the ICU population.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 6","pages":"e70152"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147932550","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":"Contemporary Immunosuppression in Simultaneous Heart-Kidney Transplantation: A United Network for Organ-Sharing Database Analysis.","authors":"Xinyi Huang, William L Baker, Paolo C Colombo, Melana Yuzefpolskaya, Douglas L Jennings","doi":"10.1002/phar.70144","DOIUrl":"10.1002/phar.70144","url":null,"abstract":"<p><strong>Background: </strong>Simultaneous heart-kidney transplantation (SHKT) has become increasingly common over the past decade, accompanied by evolving recipient characteristics and outcomes introduced by the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. However, contemporary data on immunosuppression practices in SHKT recipients remain limited. To address these knowledge gaps, this study characterizes contemporary immunosuppression practices in SHKT recipients and evaluates their association with post-transplant outcomes.</p><p><strong>Methods and results: </strong>This UNOS registry analysis included adult SHKT recipients from January 2013 to June 2025. We evaluated induction and maintenance immunosuppression strategies and 1-year outcomes including treated rejection, graft failure, infection, and mortality. Among 2634 recipients, T-cell depleting agents remained the most used induction strategy (41.3%), followed by basiliximab (36.8%) and no induction (21.9%). Basiliximab use increased post-2018, while anti-thymocyte globulin use declined. mTOR inhibitor use at 1 year was highest among patients receiving T-cell depleting agents. Despite these shifts, adjusted analyses showed no significant differences in 1-year rejection, graft failure, or mortality across induction groups.</p><p><strong>Conclusion: </strong>Contemporary SHKT recipients experience similar 1-year outcomes across induction strategies. Basiliximab may be sufficient for standard-risk SHKT recipients.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70144"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633855","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":"Incidence of Acute Kidney Injury With the Use of Nafcillin Versus Oxacillin.","authors":"Alejandro D Perez, Autumn L Brenner, Emilia Pieta, Rayce Harrison, Said Sultan, Madison G Ponder, Lindsay Daniels","doi":"10.1002/phar.70145","DOIUrl":"10.1002/phar.70145","url":null,"abstract":"<p><strong>Background: </strong>Antistaphylococcal penicillins (ASPs) are highly effective against infections caused by methicillin-susceptible Staphylococcus aureus (MSSA). Nafcillin and oxacillin are ASPs with similar spectra of activity, rates of efficacy, pharmacokinetic profiles, and cost. However, there is a growing body of evidence suggesting key distinctions between the safety profiles of nafcillin and oxacillin, including a higher rate of acute kidney injury (AKI) with nafcillin. This retrospective study aims to compare the rate of AKI with nafcillin versus oxacillin at a large academic medical center.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted including adult inpatients who were treated with at least six doses of oxacillin or nafcillin. The primary outcome was the incidence of AKI during treatment. Secondary outcomes included change in serum creatinine from baseline, AKI stage, duration of therapy, duration of hospitalization, and in-hospital mortality. Exploratory outcomes included the incidence of moderate hypokalemia, severe hypokalemia, and hepatotoxicity.</p><p><strong>Results: </strong>Among 638 patients (171 on nafcillin, 467 on oxacillin), AKI occurred in 33.3% of patients in the nafcillin group compared to 19.5% in the oxacillin group (adjusted risk ratio 1.55, 95% confidence interval 1.16-2.06; p < 0.01). Nafcillin was associated with a greater incidence of AKI at each stage, longer duration of hospitalization, higher in-hospital mortality rate, and increased rates of moderate and severe hypokalemia compared to oxacillin.</p><p><strong>Conclusion: </strong>In this study, nafcillin was associated with a significantly higher incidence of AKI than oxacillin.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70145"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717620","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":"SGLT2 Inhibitors and GLP-1 Receptor Agonists After Acute Kidney Injury: A Systematic Review With Meta-Analysis.","authors":"Erin F Barreto, Yessie A Garcia-Nieves, Evan C Johnson, Ty H Eder, Danielle J Gerberi, Kianoush B Kashani, Andrea G Kattah, Kathleen D Liu, Heather P May, Rozalina G McCoy, Daniel P Murphy, Andrew D Rule, Patrick M Wieruszewski","doi":"10.1002/phar.70137","DOIUrl":"10.1002/phar.70137","url":null,"abstract":"<p><p>Sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are nephroprotective and their use is recommended for adults with chronic kidney disease (CKD). The role of SGLT2i and GLP-1 RAs in patients with acute kidney injury (AKI) is unknown. This systematic review aimed to estimate the effect of SGLT2i or GLP-1 RAs on clinical outcomes in AKI. We systematically searched Embase, MEDLINE, Scopus, Web of Science Core Collection, and clinical trials registries for observational studies and clinical trials from database inception to July 3, 2025. Included studies evaluated adults (≥ 18 years) with AKI during a hospitalization and compared patients subsequently exposed to either SGLT2i or GLP-1 RAs to a non-exposed control group. Random effects meta-analyses were performed. Six studies related to SGLT2i (five observational, one randomized trial) and one related to GLP-1 RAs (one observational) met eligibility criteria (N = 432,048 patients). SGLT2i/GLP-1 RA exposure was associated with lower odds of major adverse kidney events (MAKE) (OR 0.63, 95% CI 0.46-0.86) and all-cause mortality [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.21-0.62] compared to controls. The odds for kidney replacement therapy were lower with SGLT2i therapy in the three studies where it was evaluated (OR 0.61, 95% CI 0.40-0.93). Sensitivity analyses restricted to SGLT2i data were consistent with the overall findings [MAKE OR 0.63 (95% CI 0.42-0.95); Mortality OR 0.34 (95% CI 0.18, 0.65)]. Exposure to SGLT2i or GLP-1 RAs after AKI, examined primarily in observational studies, was associated with improved clinical outcomes. These findings are promising and warrant evaluation in randomized clinical trials.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70137"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634069","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":"Thrombosis Across Female-Specific Malignancies: From Chemotherapy-Driven Risk to Prophylaxis and Drug Interactions.","authors":"Maryam Aghakouchakzadeh, Hessam Kakavand, Anne J Goldberg, Melissa Accordino, Meghna Trivedi, Jayant K Raikhelkar, Azita H Talasaz","doi":"10.1002/phar.70149","DOIUrl":"10.1002/phar.70149","url":null,"abstract":"<p><p>Cancer-associated thrombosis (CAT) remains a leading cause of morbidity and mortality among patients with cancer. Female-specific malignancies such as breast, ovarian, endometrial, and cervical cancers exhibit distinct thrombotic profiles driven by hormonal, anatomical, and treatment-related factors. This review summarizes current evidence on CAT in these malignancies, emphasizing chemotherapy- and hormone-related risk, thromboprophylactic strategies, and pharmacologic considerations in anticoagulant selection. Ovarian cancer carries the highest incidence of venous thromboembolism (VTE), ranging from 5% to 14%, largely due to advanced disease, ascites, and platinum-based chemotherapy. Breast cancer accounts for approximately 15% of all CAT cases, with increased risk observed among patients treated with selective estrogen receptor modulators or cyclin-dependent kinase 4/6 inhibitors. Endometrial cancer presents a moderate to high risk for CAT, especially in obese patients and those receiving hormonal therapy or radiation. Prophylaxis with low-molecular-weight heparins (LMWHs) or direct oral anticoagulants (DOACs) effectively reduces VTE incidence in high-risk patients. In the API-CAT trial, reduced-dose apixaban (2.5 mg twice daily) was non-inferior to full-dose therapy for extended anticoagulation after 6 months of treatment (2.1% vs. 2.8%; adjusted subhazard ratio, 0.76; 95% Confidence Interval (CI), 0.58-0.97; p = 0.001). Drug-drug interactions with anticoagulants and agents such as doxorubicin, ribociclib, and tamoxifen warrant individualized anticoagulant selection and close monitoring. A patient-centered pharmacotherapeutic approach, supported by multidisciplinary collaboration, is essential to optimize thrombosis prevention and minimize bleeding risk in women with cancer.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70149"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717625","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":"Association of Human Leucocyte Antigen with Tacrolimus Pharmacokinetics in Renal Transplant Patients.","authors":"Rashmi J Hemani, Amit S Joreja, Nitiraj B Shete, Ratika Srivastava, Shailesh M Soni, Shishir D Gang, Abhijit M Konnur, Umapati N Hegde, Hardik B Patel, Banibrata N Mukhopadhyay, Manan A Raval, Sachchida Nand Pandey","doi":"10.1002/phar.70141","DOIUrl":"10.1002/phar.70141","url":null,"abstract":"<p><strong>Introduction: </strong>Tacrolimus (Tac or FK-506) is an immunosuppressive agent that inhibits T-cell activation and proliferation. It has a narrow therapeutic index and shows inter-patient variabilities in its plasma concentration. Human Leucocyte Antigen (HLA) plays a major role in immune regulation and function. Tac inhibits the T-cells, and HLA antigens are expressed in T-cells. The objective of this study was to determine the role of the HLA Class I (HLA-A, HLA-B, and HLA-C) and Class II (HLA-DRB1, HLA-DQB1, and HLA-DQA1) in influencing Tac PK among renal transplant patients.</p><p><strong>Material and methods: </strong>This study included HLA genotyping data of 462 renal transplant patients. Tacrolimus blood trough concentration/dose (Co/D) was calculated on day 7 and months 1, 3, 6, and 12 post-transplantation, and the association with HLA alleles was studied. Furthermore, biopsy-proven toxicity, rejection, and pathological events were evaluated for their association with HLA alleles.</p><p><strong>Result: </strong>One-way ANOVA analysis showed that HLA-B*51:01 and HLA-C*16:02 were significantly associated with Tac Co/D at multiple time points, with a significance level of p < 0.05. In addition, HLA-DRB1*04:03 was associated with post-renal transplant toxicity [Hazard Ratio (HR) = 8.500, 95% Confidential Interval (CI) (1.517-47.619)] and pathological events [HR = 2.310, 95% CI (1.149-4.642)]. HLA-A*02:11 [HR = 3.530, 95% CI (1.074-11.601)], and HLA-DQB*03:01 [HR = 5.055, 95% CI (1.544-16.551)] were associated with high risk of transplant rejection.</p><p><strong>Conclusion: </strong>Our data suggest that HLA alleles influence the PK of Tac and affect graft survival in renal transplant patients.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70141"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633793","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":"Bayesian Dosing Simulator (BDS): A Pharmacokinetic Modeling Tool for Optimized Antibiotic Therapy.","authors":"Adrian Valadez, Marc H Scheetz, Michael N Neely, Helen K Donnelly, Erin Korth, Richard G Wunderink, Nathaniel J Rhodes","doi":"10.1002/phar.70148","DOIUrl":"10.1002/phar.70148","url":null,"abstract":"<p><strong>Background: </strong>Meropenem is widely used to treat hospital-acquired pneumonia in critically ill patients, with efficacy dependent on the time that free concentrations exceed the minimum inhibitory concentration (fT > MIC). In practice, single-sample therapeutic drug monitoring (TDM) may not ensure target attainment, particularly in patients requiring continuous renal replacement (CRRT). Model-informed precision dosing (MIPD) enables individualized, real-time adjustments, but implementation is limited. Herein, we developed a Shiny application for Bayesian meropenem dose optimization.</p><p><strong>Methods: </strong>A previously published nonparametric model was translated into a parametric Bayesian framework with maximum a posteriori (MAP) updating implemented through a Shiny interface. Plasma pharmacokinetic (PK) data from critically ill patients served for external validation. Posterior predictions were benchmarked against population and individual (MAP) outputs from Pmetrics 3.09 and population median profiles from 1000 Monte Carlo simulations per patient. Predictive performance was assessed using relative median prediction error (rMPE) and relative median absolute prediction error (rMAPE), for the combined cohort overall and stratified by CRRT status. Sparse sampling scenarios (one, two, and three observations per patient) were also evaluated.</p><p><strong>Results: </strong>Eighteen patients were evaluated (non-CRRT n = 13; CRRT n = 5). In Pmetrics, rMPE ranged from -7.7% to 9.4% and rMAPE from 18.5% to 25.5% across renal replacement strata and prediction types. Simulation-based population predictions yielded greater error, with rMPE/rMAPE of -25%/34% in CRRT patients and -21%/30% in non-CRRT patients. Across Bayesian Dosing Simulator (BDS) sampling scenarios, prediction error remained within prespecified limits (rMPE ±20%, rMAPE ≤ 30%), with F20 ranging from 80% to 94% and F30 from 87% to 94%.</p><p><strong>Conclusion: </strong>A validated nonparametric meropenem model was successfully implemented within an open-source Bayesian framework yielding predictive accuracy comparable to the reference model with robust performance under sparse sampling, supporting its feasibility for individualized meropenem dosing. Prospective evaluation of its clinical safety and effectiveness is needed.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70148"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778373","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":"Treatment Adherence to Oral Direct-Acting Antiviral Agents in Hepatitis C Infection.","authors":"Javeria Khalid, Jieni Li, Rajender R Aparasu","doi":"10.1002/phar.70126","DOIUrl":"10.1002/phar.70126","url":null,"abstract":"<p><strong>Background: </strong>Optimal adherence to second-generation direct-acting antiviral agents (DAAs) is crucial for preventing disease progression and reducing treatment resistance in patients with Hepatitis C virus (HCV). Therefore, we examined DAA adherence and its predictors in patients with HCV.</p><p><strong>Study design: </strong>Retrospective cohort study.</p><p><strong>Methods: </strong>The study cohort included adult patients with HCV in the Merative MarketScan databases from 2017 to 2019. Incident DAA users were selected with a 12-month baseline continuous enrollment. Adherence was assessed during the 8- to 24-week follow-up period, as per guidelines, using two adherence metrics: the proportion of days covered (PDC ≥ 80%) and the completion of therapy (≤ 14-day gap). Predictors of non-adherence were assessed by multivariable logistic regression based on the Andersen Behavioral Model. Sensitivity analysis was conducted at PDC ≥ 70% and ≥ 90%, and a gap of ≤ 21 days.</p><p><strong>Results: </strong>Among 3412 incident DAA users, 84.79% of patients were adherent (PDC ≥ 80%), and 84.23% of patients completed the treatment without a significant gap (≥ 14 days). Several predictors were associated with non-adherence and were consistent for both adherence metrics. Older age (55-64 years, adjusted odds ratio [aOR]: 0.50, 95% Confidence Interval [CI]: 0.35-0.70) and middle-aged adults (45-54 years, aOR: 0.53, 95% CI: 0.37-0.75) were less likely to be non-adherent. High monthly out-of-pocket (OOP) costs (≥ $400) increased the risk of non-adherence (aOR: 1.25, 95% CI: 1.02-1.54). Patients with cirrhosis (compensated: aOR: 3.85, 95% CI: 2.99-4.94; decompensated: aOR: 3.02, 95% CI: 1.95-4.70), HIV infection (aOR: 1.83, 95% CI: 1.06-3.18), and substance use disorder (aOR: 1.38, 95% CI: 1.01-1.89) were found to have higher odds of being non-adherent. Patients who were prescribed the velpatasvir/sofosbuvir regimen were less likely to be non-adherent (aOR: 0.78, 95% CI: 0.62-0.99). Sensitivity analysis yields similar findings.</p><p><strong>Conclusions: </strong>Overall adherence to DAA therapy was high in HCV; however, several clinical and non-clinical factors were associated with non-adherence. Findings from this study can inform the development of targeted interventions to optimize DAA adherence in HCV.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70126"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634006","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":"Impact of Dosing Interval Adherence on Pharmacokinetic Outcomes of Recombinant Erwinia Asparaginase in Pediatric Leukemia or Lymphoma.","authors":"Milre M Matherne, John C Panetta, Jaclyn Hopp, Hiroto Inaba, Ching-Hon Pui, Seth E Karol, M Brooke Bernhardt, Hope D Swanson","doi":"10.1002/phar.70146","DOIUrl":"10.1002/phar.70146","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment for pediatric acute lymphoblastic leukemia includes asparaginase as an integral component of therapy. Hypersensitivity reactions or silent inactivation to Escherichia coli (E. coli) formulations may necessitate switching to Erwinia-based asparaginase (asparaginase Erwinia chrysanthemi [E-ASP] or recombinant asparaginase Erwinia chrysanthemi [R-ASP]). However, pharmacokinetic data for R-ASP in pediatrics remain limited, and recommended dosing schedules present logistical challenges. We investigated if adherence to approved dosing regimens for R-ASP is necessary to achieve optimal pharmacokinetic exposure in pediatric patients with leukemia or lymphoma.</p><p><strong>Methods: </strong>We performed a single institution, retrospective review of pharmacokinetic data in patients who received R-ASP between October 1, 2021 and September 30, 2024. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to evaluate asparaginase pharmacokinetic activity. The pharmacokinetic model was used to determine if the labeled dosing window for R-ASP is required to achieve effective asparagine depletion.</p><p><strong>Results: </strong>Twenty-six patients with 115 measurements of serum asparaginase activity (SAA) were included in the analysis. Based on model simulations from our pediatric patient data, maintaining SAA ≥ 0.1 IU/mL in 90% of patients throughout the dosing interval with R-ASP 25/25/50 mg/m² administered intramuscularly on Monday, Wednesday, and Friday requires precise timing. Specifically, the Friday 50 mg/m² dose must be administered within 58 h of the Wednesday morning dose to sustain therapeutic activity. Additionally, only 62.5% of patients maintained SAA ≥ 0.1 IU/mL at 72 h after the last dose with R-ASP 25 mg/m² administered intramuscularly on a Monday, Wednesday, and Friday dosing schedule.</p><p><strong>Conclusion: </strong>Overall, our findings support the importance of adhering closely to the United States Food and Drug Administration approved dosing schedule for R-ASP to ensure adequate asparaginase activity in pediatric patients with leukemia or lymphoma.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 5","pages":"e70146"},"PeriodicalIF":4.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729612","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}