Pharmacotherapy最新文献

{"title":"Women's Health in Oncology.","authors":"Janelle Perkins","doi":"10.1002/phar.70189","DOIUrl":"10.1002/phar.70189","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 8","pages":"e70189"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448665","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":"Getting It Right the Second Time: How Can we Optimize First-Generation Cephalosporin Dosing for Skin and Soft Tissue Infections in the 21st Century?","authors":"Jonathan H Ryder, Shawnalyn W Sunagawa, Nathaniel J Rhodes, Trevor C Van Schooneveld, Jeremy E Tigh, Sean N Avedissian, Nicolas Cortes-Penfield","doi":"10.1002/phar.70179","DOIUrl":"10.1002/phar.70179","url":null,"abstract":"<p><p>Optimal cephalexin and cefadroxil dosing for skin and soft tissue infections (SSTIs) is unclear. We summarize clinical and pharmacokinetic/pharmacodynamic (PK/PD) data that compare dosing strategies for SSTIs. Additionally, we conduct population PK target attainment simulations for varying doses of cephalexin and cefadroxil for Staphylococcus aureus and Group A Streptococcus. Although some clinical data support lower doses in mild SSTIs, higher doses optimize PK/PD parameters in moderate-severe SSTIs, especially due to Staphylococcus aureus. Further prospective clinical and PK/PD studies, especially in obese adults, would be beneficial.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 7","pages":"e70179"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13254493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148219182","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":"Comment on \"Pharmacokinetic Analysis of Intravenous Push Cefepime in Critically Ill Patients With Sepsis\".","authors":"Maajid Mohi Ud Din Malik, Rajesh Prasad Jayaswal","doi":"10.1002/phar.70186","DOIUrl":"https://doi.org/10.1002/phar.70186","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 7","pages":"e70186"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391580","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":"Quantifying the Serum Magnesium Response and Predictors of Response Following Intravenous Magnesium Replacement in Critically Ill Patients.","authors":"Naheel Said, Giovani Angelotti, Wedad Awad, Asma'a Al-Kharabsheh, An-Kwok Ian Wong, Lama Nazer","doi":"10.1002/phar.70175","DOIUrl":"10.1002/phar.70175","url":null,"abstract":"<p><strong>Background and objective: </strong>Intravenous magnesium is commonly used in critically ill patients; however, data on the serum level response following its administration are limited. This study aimed to evaluate serum magnesium changes after administration of intravenous magnesium sulfate (IV-MgSO₄) and identify predictors of a greater response among critically ill patients.</p><p><strong>Methodology: </strong>This retrospective multicenter study included adult critically ill patients from the Medical Information Mart for Intensive Care IV and eICU databases. Patients were included if they received IV-MgSO₄ and had serum magnesium measured within 36 h before and after administration. Patients receiving renal replacement therapy, total parenteral nutrition, magnesium-containing intravenous fluids, or oral magnesium supplementation were excluded. Linear regression analyses were performed to identify predictors of greater magnesium response.</p><p><strong>Results: </strong>The study included 25,637 patients who received 54,556 doses of IV-MgSO₄. The mean age was 62.8 ± 16.5 Standard deviation years, and 13,180 (51.4%) were females. The most common intensive care unit admission diagnoses were cardiovascular (n = 7399; 28.9%) and respiratory (n = 4245; 16.6%). Baseline magnesium levels were normal in 39,149 (71.8%) episodes, mild-to-moderate hypomagnesemia in 13,588 (24.9%), and severe hypomagnesemia in 1819 (3.3%). Median serum magnesium increased by 0.15 mg/dL (interquartile range (IQR) 0.05-0.25) per 1 g of IV-MgSO₄ administered, and the greatest increase was observed in patients with severe hypomagnesemia (median [IQR]: 0.25 mg/dL [0.10-0.50]), followed by mild-to-moderate hypomagnesemia (median [IQR]: 0.22 mg/dL [0.10-0.40]). Predictors of greater response to IV-MgSO₄ were lower initial magnesium (β = 0.2035; 95% confidence interval (CI): 0.193 to 0.214; p < 0.001) and reduced renal function (β = 0.2557; 95% CI: 0.212 to 0.300; p < 0.001).</p><p><strong>Conclusion: </strong>Among a large cohort of critically ill patients, 1 g of IV-MgSO₄ was associated with a median serum magnesium increase of 0.15 mg/dL. Lower initial magnesium and reduced renal function were predictors of greater serum magnesium increase with intravenous replacement.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 7","pages":"e70175"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148212148","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":"Response to Comment on \"Pharmacokinetic Analysis of Intravenous Push Cefepime in Critically Ill Patients With Sepsis\".","authors":"Susan E Smith, Christopher M Bland, Trisha N Branan","doi":"10.1002/phar.70187","DOIUrl":"https://doi.org/10.1002/phar.70187","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 7","pages":"e70187"},"PeriodicalIF":4.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391550","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":"Hyperfiltration in Critically Ill Older Adults: Incidence, Risk Factors, Time Course, and Predictive Performance of Kidney Function Estimation.","authors":"Ryusei Mikami, Shungo Imai, Mineji Hayakawa, Gaku Izumi, Hitoshi Kashiwagi, Yuki Sato, Shunsuke Nashimoto, Takeshi Wada, Mitsuru Sugawara, Yoh Takekuma","doi":"10.1002/phar.70153","DOIUrl":"10.1002/phar.70153","url":null,"abstract":"<p><strong>Study objective: </strong>This study aimed to evaluate the incidence, associated risk factors, time course, and predictive performance of kidney function estimation equations for hyperfiltration in critically ill older adults.</p><p><strong>Methods: </strong>This retrospective observational study evaluated 325 patients (median age, 76 years) admitted to the intensive care unit (ICU) of a tertiary-care university hospital, for a total of 2934 patient-days. The hyperfiltration threshold was defined using measured creatinine clearance (Clcr) > -0.883 × age + 167.398. Independent factors associated with hyperfiltration were identified via a multivariable logistic regression model, and time to onset and duration were evaluated using Kaplan-Meier curves. Additionally, the predictive performance of the measured Clcr was assessed using the Cockcroft-Gault equation. Bias was analyzed using the Bland-Altman analysis, and accuracy was evaluated using the percentage within 30% of the measured Clcr (P30).</p><p><strong>Results: </strong>Hyperfiltration occurred in 56% of the patients. Risk factors included male sex, high body mass index, trauma-related admission, vasopressor use, and low serum creatinine levels. The median time from ICU admission to hyperfiltration onset was 5 days, and the median duration of hyperfiltration episodes was 8 days. The Cockcroft-Gault equation substantially underestimated measured Clcr in patients with hyperfiltration. Even among those whose measured Clcr did not meet the conventional augmented renal clearance (ARC) threshold (> 130 mL/min), the equation exhibited a clinically significant negative bias (-35 mL/min) with limited accuracy (P30: 39%). This underestimation was even more pronounced in patients meeting the ARC criteria (bias: -62 mL/min; P30: 27%).</p><p><strong>Conclusions: </strong>Hyperfiltration is highly prevalent in critically ill older adults. The Cockcroft-Gault equation substantially underestimated actual kidney function, even without meeting the ARC criteria. Continuous monitoring of the measured Clcr is recommended to avoid inappropriate medication dose reductions due to underestimation.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 6","pages":"e70153"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874986","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":"Factors That Influence Blood Pressure Changes With the Use of Sodium-Glucose Cotransporter 2 Inhibitors in People With Type 2 Diabetes.","authors":"Sara Salama, Charlotte Bolch, Dejan Landup, Elizabeth Van Dril, Christie Schumacher","doi":"10.1002/phar.70156","DOIUrl":"10.1002/phar.70156","url":null,"abstract":"<p><strong>Study objective: </strong>Multiple clinical trials have reported variable reductions in blood pressure with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Given the variability in the magnitude of blood pressure reduction observed across studies, there is interest in understanding how patient-specific factors influence the blood pressure-lowering effects of SGLT2 inhibitors. The primary objective of this study was to evaluate factors that influence blood pressure changes in people with type 2 diabetes when an SGLT2 inhibitor is initiated.</p><p><strong>Design: </strong>Multicenter retrospective cohort chart review.</p><p><strong>Data source: </strong>Patients were selected through an electronic medical record-generated report between January 1, 2013, and September 30, 2019.</p><p><strong>Patients: </strong>Adults (≥ 18 years) receiving care within Advocate Medical Group were included if they had a documented diagnosis of type 2 diabetes and had been prescribed one of four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin) for at least 7 days.</p><p><strong>Results: </strong>In 1,422 patients, mean systolic blood pressure (SBP) decreased by 4.1 mmHg (range -58.7 to 58.0), and mean diastolic blood pressure (DBP) decreased by 2.1 mmHg (range -44.7 to 29.0) after SGLT2 inhibitor initiation. Significant blood pressure reductions occurred only in patients with elevated baseline blood pressure, with greater declines at higher baseline pressures (p < 0.001). Patients with baseline SBP > 160 mmHg showed a mean reduction of 26.7 mmHg, whereas those with SBP < 120 mmHg had a mean increase of 6.1 mmHg. DBP followed a similar pattern: Individuals with baseline DBP > 100 mmHg had a mean reduction of 16.0 mmHg, whereas those with DBP < 60 mmHg experienced a mean increase of 10.7 mmHg.</p><p><strong>Conclusion: </strong>Blood pressure responses to SGLT2 inhibitors were driven by baseline blood pressure, with the greatest reductions observed in patients with elevated blood pressure at initiation. Individuals with lower starting pressures showed minimal change or slight increases, indicating a normalizing effect rather than uniform blood pressure lowering with initiation of SGLT2 inhibitors. These findings support incorporating baseline blood pressure into treatment selection to optimize cardiovascular risk management in patients with type 2 diabetes.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 6","pages":"e70156"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147932527","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":"Predictors and Clinical Outcomes of Long-Term Opioid Therapy in Older Adults: A Systematic Review.","authors":"Iftekhar Ahmed, Nina E Teo, Noha Keshk, David R Foster","doi":"10.1002/phar.70151","DOIUrl":"10.1002/phar.70151","url":null,"abstract":"<p><strong>Introduction: </strong>Older adults have a higher prevalence of pain and are more likely to receive long-term opioid therapy (LTOT) compared to other age groups. They are also at elevated risk of opioid-related adverse events due to physiological changes and polypharmacy. This systematic review aimed to identify predictors and clinical outcomes associated with LTOT in older adults.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and Cochrane Library to identify randomized clinical trials (RCT) and observational studies published from inception until July 31, 2025. We included studies that examined opioid use for ≥ 90 days and included participants aged ≥ 60 years. Data were synthesized using harvest plots and narrative synthesis. The Newcastle-Ottawa Scale was used for risk of bias assessment.</p><p><strong>Results: </strong>Forty-one observational studies were included; no RCTs met the inclusion criteria. Patient-related factors associated with LTOT across most studies were low income/wealth (n = 6/6 studies), depressive disorders (n = 6/9 studies), and dual insurance eligibility/enrollment (n = 4/6 studies). Prescription/dispensation-related factors associated with LTOT across most studies were opioid use before surgery/trauma (n = 6/6 studies), prior/concurrent use of benzodiazepines (n = 6/6 studies), anxiolytics/sedatives/hypnotics (n = 3/4 studies), anticonvulsants (n = 3/4 studies), opioid use after surgery/trauma (n = 3/3 studies), long-acting opioids (n = 3/3 studies), and longer duration of initial opioid (n = 2/2 studies). Regarding outcomes of LTOT, most studies reported positive associations between LTOT and hospital readmission/emergency department visit (n = 3/4 studies), revision surgery (n = 2/2 studies), health care costs (n = 2/2 studies), opioid overdose (n = 1/1 study), and falls (n = 1/1 study). Evidence on the association of LTOT with mortality and fractures was inconclusive.</p><p><strong>Conclusions: </strong>This systematic review identified several predictors and adverse outcomes associated with LTOT in older adults. However, no evidence exists regarding the effectiveness of LTOT for pain management in this population. Prospective studies with long-term follow-up are needed to address this gap and inform benefit-harm assessment of LTOT in clinical practice.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 6","pages":"e70151"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869267","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":"Continuous Subcutaneous Ketamine Infusion May Induce Tacrolimus and Sirolimus Clearance: A Case Report.","authors":"Jana Stojanova, Bridin Murnion, Fay Burrows, Lilibeth Carlos, Tomoyuki Mizuno, Takanobu Nadai, Kei Irie, Nuala Helsby, Kavitha Muthiah, Richard Day","doi":"10.1002/phar.70150","DOIUrl":"10.1002/phar.70150","url":null,"abstract":"<p><strong>Background: </strong>Drug interactions involving immunosuppressants can compromise transplant outcomes. Although repeated ketamine administration induces hepatic enzymes in experimental models, clinical reports of induced clearance of cytochrome P450 (CYP) substrates are lacking. Continuous subcutaneous ketamine infusions are increasingly used for acute pain management. We present a case of difficult-to-maintain tacrolimus and sirolimus concentrations in the context of subcutaneous ketamine infusion for acute pain management.</p><p><strong>Methods: </strong>A 55-year-old male heart transplant recipient received continuous subcutaneous ketamine (5.2-10.4 mg/h) for pain management following lower limb thrombectomy. Tacrolimus and sirolimus concentrations were monitored throughout hospitalization and rehabilitation. Population pharmacokinetic modeling with Bayesian estimation characterized temporal clearance changes, incorporating inter-occasion variability across six periods (pre-, during-, and weekly post-ketamine administration for 4 weeks).</p><p><strong>Results: </strong>Following ketamine initiation, tacrolimus and sirolimus concentrations remained subtherapeutic despite dose escalations of 1.8-fold and 5-fold, respectively. Pharmacokinetic modeling revealed approximately 2-fold clearance increases during ketamine administration, peaking 1 week after initiation. Following ketamine discontinuation, tacrolimus and sirolimus concentrations progressively increased over 3 weeks, consistent with enzyme induction and recovery. Drug Interaction Probability Scale assessment indicated probable interaction (score + 5). Brief concomitant flucloxacillin use may have contributed to the observed changes.</p><p><strong>Conclusions: </strong>This case provides preliminary evidence of potential interaction between ketamine and CYP3A4-metabolized immunosuppressants. Clinicians should consider increased therapeutic drug monitoring when using ketamine with narrow therapeutic range medications, continuing approximately 3 weeks post-discontinuation.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 6","pages":"e70150"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13160711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147875019","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":"Cancer Treatment Modalities and Female Fertility Preservation.","authors":"Seonga Song, Lilia Davenport, Samantha Paone, Jamie Chin-Hon","doi":"10.1002/phar.70143","DOIUrl":"10.1002/phar.70143","url":null,"abstract":"<p><p>Oncofertility is the practice of joining oncology clinicians with reproductive endocrinologists to assess patients' tumor biology, tumor stage, and mutation analysis to discuss the infertility risks from tumor-directed treatments and provide fertility preservation opportunities to patients who will undergo or have received tumor-directed therapy since cancer treatments can affect fertility. Tumor-directed therapies, such as radiation and antineoplastic agents, have greatly expanded beyond traditional deoxyribonucleic acid (DNA)-damaging agents to encompass pharmacologic agents, such as targeted monoclonal antibodies, kinase inhibitors, and immune activating therapies that may have varying effects on women's fertility. Here, we review the current literature to provide a comprehensive summary on the effect of cancer treatment modalities on female fertility, fertility preservation options in female patients, and the role of pharmacists in oncofertility practice.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 6","pages":"e70143"},"PeriodicalIF":4.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874956","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}