Pharmacotherapy最新文献

{"title":"Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction.","authors":"Kelli Henry, Shiyuan Deng, Xianyan Chen, Tianyi Zhang, John Devlin, David Murphy, Susan Smith, Brian Murray, Rishikesan Kamaleswaran, Amoreena Most, Andrea Sikora","doi":"10.1002/phar.4642","DOIUrl":"https://doi.org/10.1002/phar.4642","url":null,"abstract":"<p><strong>Background: </strong>Fluid overload (FO) in the intensive care unit (ICU) is common, serious, and may be preventable. Intravenous medications (including administered volume) are a primary cause for FO but are challenging to evaluate as a FO predictor given the high frequency and time-dependency of their use and other factors affecting FO. We sought to employ unsupervised machine learning methods to uncover medication administration patterns correlating with FO.</p><p><strong>Methods: </strong>This retrospective cohort study included 927 adults admitted to an ICU for ≥72 h. FO was defined as a positive fluid balance ≥7% of admission body weight. After reviewing medication administration record data in 3-h periods, medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess their temporal association with FO.</p><p><strong>Results: </strong>FO occurred in 127 (13.7%) of 927 included patients. Patients received a median (interquartile range) of 31(13-65) discrete intravenous medication administrations over the 72-h period. Across all 47,803 intravenous medication administrations, 10 unique medication clusters, containing 121 to 130 medications per cluster, were identified. The mean number of Cluster 7 medications administered was significantly greater in the FO cohort compared with patients without FO (25.6 vs.10.9, p < 0.0001). A total of 51 (40.2%) of 127 unique Cluster 7 medications were administered in more than five different 3-h periods during the 72-h study window. The most common Cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of Cluster 7 medications to an FO prediction model including the Acute Physiologic and Chronic Health Evaluation (APACHE) II score and receipt of diuretics improved model predictiveness from an Area Under the Receiver Operation Characteristic (AUROC) curve of 0.719 to 0.741 (p = 0.027).</p><p><strong>Conclusions: </strong>Using machine learning approaches, a unique medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict FO compared to traditional prediction models. Integration of this approach into real-time clinical applications may improve early detection of FO to facilitate timely intervention.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922584","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":"Associating regulatory actions on diclofenac use with Danish trends in utilization by route of administration 1999-2023.","authors":"Anna Emilie Møller, Anne Bech-Drewes, Lotte Rasmussen, Søren Friis, Morten Schmidt","doi":"10.1002/phar.4643","DOIUrl":"https://doi.org/10.1002/phar.4643","url":null,"abstract":"<p><strong>Aims: </strong>With the growing evidence of cardiovascular risks associated with diclofenac use, regulatory measures governing its application and sales have intensified since 2008. We evaluated the association between central regulatory actions and trends in diclofenac use in Denmark from 1999 to 2023, according to different dosage forms and routes of administration.</p><p><strong>Methods and results: </strong>Data on diclofenac sales in Denmark from 1999 to 2023 were retrieved from the publicly available web database MEDSTAT, based on the Danish Register of Medicinal Products Statistics. The annual sales of various diclofenac dosage forms, including systemic (tablets, modified-release dosage forms, and suppositories) and topical (nonspecific and ophthalmic) dosage forms, were calculated and displayed by sales unit. From 1999 to 2008, sales of all systemically administered diclofenac forms increased: tablets by 51% (2000-2008), modified-release dosage forms by 40% (2003-2007), and suppositories by 44% (1999-2008). Thereafter, sales of tablets declined by 86% and modified-release dosage forms by 90% through 2023. The sales of suppositories declined somewhat lesser, by 34%, during 2008 to 2018 and then increased by 67% through 2023. Sales of nonspecific topical diclofenac increased by several thousandfold from 2005, although with brief periods of decline.</p><p><strong>Conclusion: </strong>Sales of systemically administered diclofenac dosage forms, particularly tablets and modified-release drugs, declined by approximately 90% from about 2008 to 2023, indicating compliance with Danish and international regulatory actions. Conversely, sales of topically administered diclofenac increased heavily from 2005 to 2023, denoting a policy-driven shift toward these lower risk dosage forms.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915448","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":"Evaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia.","authors":"Rachel D Harris, Olga A Taylor, M Monica Gramatges, Amy E Hughes, Mark Zobeck, Sandi Pruitt, M Brooke Bernhardt, Ashley Chavana, Van Huynh, Kathleen Ludwig, Laura Klesse, Kenneth Heym, Timothy Griffin, Rodrigo Erana, Juan Carlos Bernini, Ashley Choi, Yuu Ohno, Melissa A Richard, Alanna C Morrison, Han Chen, Bing Yu, Philip J Lupo, Karen Rabin, Michael E Scheurer, Austin L Brown","doi":"10.1002/phar.4638","DOIUrl":"https://doi.org/10.1002/phar.4638","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.</p><p><strong>Methods: </strong>This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States. Clinical information was abstracted from medical records. Suspected neurotoxic events occurring within 21 days of intravenous and/or intrathecal methotrexate delivered between the end of induction and start of maintenance therapy were independently reviewed by at least two pediatric oncologists. Germline DNA was genotyped and 97 methotrexate pharmacogenomic variants of interest with at least grade 3 evidence were identified using the Pharmacogenomics Knowledge Base. Associations between variants and neurotoxicity were assessed by logistic regression. Data were randomly split (80/20) and random forest was constructed to estimate the ability of the variants to correctly classify neurotoxicity.</p><p><strong>Results: </strong>Of the 763 patients included in the study, 8.2% (n = 63) developed methotrexate-associated neurotoxicity. In logistic models, none of the 97 available pharmacogenomic variants reached adjusted statistical significance. However, two variants, rs17222723 (odds ratio [OR] = 2.83 [ref. = T allele], 95% confidence interval [CI]: 1.20-6.15) in ABCC2 and rs1045642 (OR = 0.66 [ref. = minor A allele], 95% CI: 0.44-0.98) in ABCB1, were nominally associated (p-value < 0.05) with neurotoxicity susceptibility. The addition of pharmacogenomic variants did not improve the predictive performance of random forest model (AUC = 0.73) compared to clinical information alone (AUC = 0.74).</p><p><strong>Conclusion: </strong>Overall, our results suggest that associations between neurotoxicity susceptibility and methotrexate pharmacogenomic variants are generally modest and these variants do not significantly improve neurotoxicity risk stratification among children with ALL.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903421","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":"The effect of carbamazepine, a strong CYP3A inducer, on the pharmacokinetics of zongertinib in healthy male volunteers.","authors":"Xiaofan Tian, Habib Esmaeili, David Minich, Friedeborg Seitz, Philipp M Roessner, Sven Wind, Rolf Grempler, Guanfa Gan, Tom S Chan, Mazyar Mahmoudi, Behbood Sadrolhefazi, Fabian Müller","doi":"10.1002/phar.4641","DOIUrl":"https://doi.org/10.1002/phar.4641","url":null,"abstract":"<p><strong>Introduction: </strong>Zongertinib (BI 1810631) is a potent, selective, and epidermal growth factor receptor (EGFR) wild-type sparing human epidermal growth factor receptor 2 (HER2) inhibitor. Based on in vitro data, the oxidative hepatic metabolism of zongertinib is principally driven by cytochrome P450 (CYP) 3A4/5. Therefore, zongertinib may be affected by strong CYP3A inducers, like carbamazepine.</p><p><strong>Objective: </strong>This study aimed to investigate the effect of multiple oral doses of carbamazepine on the pharmacokinetics of a single oral dose of zongertinib in healthy male subjects.</p><p><strong>Methods: </strong>This open-label, two-period, fixed-sequence clinical drug-drug interaction study examined the pharmacokinetics of a single 60-mg oral dose of zongertinib in the absence or presence of multiple oral doses of carbamazepine. The extent of drug-drug interaction was estimated using the adjusted geometric mean ratios (and 90% confidence intervals [CIs]) for the test treatment (zongertinib in the presence of carbamazepine) versus the reference treatment (zongertinib alone) for areas under the plasma concentration-time curve from time 0 to infinity and to the last quantifiable time point (AUC_0-∞, AUC_0-tz) and maximum measured plasma concentration (C_max).</p><p><strong>Results: </strong>Sixteen subjects (all Caucasian males) received zongertinib alone in Study Period 1, and 15 of them received both zongertinib and carbamazepine in Study Period 2. Upon co-administration with carbamazepine in Study Period 2, AUC_0-∞ and AUC_0-tz of zongertinib were both reduced to 36.5% (90% CI: 32.0%-41.6% for AUC_0-∞ and 31.9%-41.7% for AUC_0-tz). The C_max of zongertinib was reduced to 56.4% (90% CI: 45.1%-70.6%).</p><p><strong>Conclusion: </strong>Zongertinib exposure was reduced by 63.5% when coadministered with the strong CYP3A inducer, carbamazepine.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896524","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":"Disease-modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications.","authors":"Erika L Hellenbart, Heather J Ipema, Mary C Rodriguez-Ziccardi, Hema Krishna, Robert J DiDomenico","doi":"10.1002/phar.4639","DOIUrl":"https://doi.org/10.1002/phar.4639","url":null,"abstract":"<p><p>Transthyretin amyloidosis (ATTR) is a rare disease that results in amyloid fibril misfolding and deposition in multiple organs, including the heart, leading to the development of ATTR cardiomyopathy (ATTR-CM), which is associated with poor outcomes. In the last decade, several disease-modifying medications are in advanced stages of clinical development or have been approved to treat ATTR-CM. The purpose of this review is to critically evaluate clinical trial data investigating the use of approved and investigational medications for the treatment of ATTR-CM. We performed a comprehensive literature search via PubMed and EMBASE to identify randomized controlled trials evaluating medications for the treatment of ATTR-CM published through August 2024. This narrative review describes the pathophysiology of ATTR-CM, highlights important screening and diagnostic work-up, and summarizes the existing clinical evidence resulting from our literature search. Several classes of disease-modifying medications are in development for ATTR-CM. The tetramer stabilizers and transthyretin silencers have proven to be the most effective therapies to date. Tafamidis and acoramidis are currently approved for ATTR-CM while vutrisiran approval for ATTR-CM may be forthcoming. Other disease-modifying medication classes in development include antisense oligonucleotides, gene editing therapies, and monoclonal antibodies. However, several unmet needs exist including the lack of cost-effectiveness due to the extremely high acquisition costs of these medications. Disease-modifying medications approved and in development to treat ATTR-CM offer hope for patients with this disease, but their lack of affordability is the biggest barrier to their use.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877615","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":"Current and emerging PCSK9-directed therapies to reduce LDL-C and ASCVD risk: A state-of-the-art review.","authors":"Candice L Garwood, Katherine P Cabral, Roy Brown, Dave L Dixon","doi":"10.1002/phar.4635","DOIUrl":"https://doi.org/10.1002/phar.4635","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Lowering low-density lipoprotein cholesterol (LDL-C) levels is a primary strategy to reduce ASCVD risk. Although statin therapy remains the initial therapy of choice to reduce LDL-C and ASCVD risk, statin intolerance and suboptimal LDL-C lowering response prompts the need for additional non-statin therapies. Ezetimibe and bempedoic acid are reasonable options but they modestly reduce LDL-C levels (15% to 25%). Therapies directed at the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, however, reduce LDL-C levels by 50%-60% when added to background statin therapy. PCSK9 is an enzyme synthesized by the liver that facilitates the degradation of LDL receptors and prevents their recycling to the hepatocyte surface to remove LDL-C from circulation. Approaches to inhibit this effect have centered on monoclonal antibodies (mAbs) (alirocumab, evolocumab) targeting PCSK9 functionality and small interfering RNA (siRNA) therapies (inclisiran) targeting the hepatic synthesis of PCSK9. Randomized controlled trials have demonstrated beneficial cardiovascular outcomes of PCSK9 mAbs, but such evidence is not yet available for inclisiran. Current clinical practice guidelines generally recommend PCSK9-directed therapies for higher-risk patients with established ASCVD and those with familial hypercholesterolemia. This approach is, in part, due to their cost and uncertain economic value, but also because these therapies require subcutaneous administration, which is not preferred by some patients. Oral therapies targeting PCSK9 are, however, in development. This scoping review covers the development of current and emerging PCSK9-directed therapies, their efficacy, safety, and role in clinical practice.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829728","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 atrial fibrillation with lamotrigine: An observational cohort study.","authors":"Sodam Kim, Landon Welch, Bertha De Los Santos, Przemysław B Radwański, Mark A Munger, Kibum Kim","doi":"10.1002/phar.4633","DOIUrl":"https://doi.org/10.1002/phar.4633","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced atrial fibrillation (AF) is recognized as an important causal association. Lamotrigine (LTG) is a widely prescribed neurological agent with Class IB antiarrhythmic properties at therapeutically relevant concentrations. The United States Food and Drug Administration has issued a warning for a higher risk of LTG proarrhythmic events in patients with structural heart disease (SHD) and/or myocardial ischemia. This study evaluated the incidence of AF with LTG use.</p><p><strong>Methods: </strong>A retrospective observational study was performed using a large healthcare claims database of adult participants analyzing 2 years AF incidence. The analytic cohort included adult participants with bipolar I disorder (BPD), partial seizures (PSZ), or generalized tonic-clonic seizures (GTSZ). Exposure to LTG was compared with commonly prescribed alternative agents as the control comparators (CTR). Participants were free from supraventricular or ventricular arrhythmias during the 6 months baseline period prior to the index LTG or CTR date. Kaplan-Meier estimator calculated 2 years cumulative AF incidence, with participants censored at last enrollment, treatment switching, or discontinuation. The AF association hazard ratios (HR) for LTG versus CTR were adjusted for baseline characteristics.</p><p><strong>Results: </strong>The analytic cohort with BPD, PSZ, and GTSZ consisted, respectively, of 150,470 LTG versus 204,704 CTR, 9565 LTG versus 21,595 CTR, and 5505 LTG versus 15,513 CTR patients. In a predominantly middle-aged female population at baseline, the prevalence of cardiovascular conditions was low. The 12 months cumulative incidence of AF for LTG versus CTR was 0.764% versus 0.642% among BPD, 0.833% versus 0.646% among PSZ, and 0.585% versus 0.338% among GTSZ, respectively. The adjusted 365-day HR [95% confidence interval CI] of AF for LTG versus CTR in the BPD, PSZ, and CTSZ groups was 1.257 [1.088-1.453], 1.651 [1.104-2.468], and 1.451 [0.770-2.734], respectively.</p><p><strong>Conclusions: </strong>In adult AF-naïve participants, LTG has a strong association with increased AF risk compared with commonly prescribed alternatives.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822328","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":"Pharmacokinetics of cefiderocol in a patient with carbapenem-resistant Acinetobacter baumannii ventriculitis: A case report.","authors":"Natalie A Finch, Alejandro Granillo, Nazanin Pouya, Adarsh Bhimraj, William R Miller, Vincent H Tam","doi":"10.1002/phar.4632","DOIUrl":"https://doi.org/10.1002/phar.4632","url":null,"abstract":"<p><strong>Objective: </strong>Cefiderocol is a novel antibiotic used to treat multidrug-resistant bacterial infections. However, there is limited data on its effectiveness for ventriculitis. The objective of this study was to evaluate cefiderocol concentrations in both serum and cerebrospinal fluid (CSF) during the treatment of ventriculitis.</p><p><strong>Method: </strong>A 54-year-old patient with carbapenem-resistant Acinetobacter baumannii ventriculitis was given cefiderocol intravenously 2 g every 6 h (each dose administered over 3 h). Serial samples were obtained over a dosing interval at steady state, and cefiderocol concentrations in serum and CSF were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cefiderocol serum concentration-time profile was characterized by a one-compartment model with zero-order input. Penetration into CSF was estimated as the CSF AUC/unbound serum AUC ratio.</p><p><strong>Results: </strong>Observed total serum concentrations ranged between 24.6 and 76.7 mg/L, while CSF concentrations were approximately 10.0 mg/L. The AUC_0-6 of the free drug in serum and CSF were 181.6 and 60.2 mg h/L, respectively.</p><p><strong>Conclusion: </strong>We observed minimal fluctuation of cefiderocol concentrations in CSF, questioning the conventional reliance on CSF/serum area under the curve (AUC) ratio as a measure of CNS penetration. Our experience suggests that a single CSF concentration (random or trough) could be directly compared to the minimum inhibitory concentration, offering a potentially simpler approach to evaluate dosing adequacy.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771233","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":"Scoping review of drug dosing recommendations in sustained low-efficiency dialysis.","authors":"Nicholas R Nelson, Nicholas J Quinn, Stephanie Bills, Alexander Dellabella, Sarah E Gregar, Alyssa Lear, Legacy Marsolek, Crystal Mounce, Morgan Tobin","doi":"10.1002/phar.4628","DOIUrl":"10.1002/phar.4628","url":null,"abstract":"<p><p>The objective of this scoping review was to answer the question, \"What has been published describing drug dosing in sustained low-efficiency dialysis (SLED)?\" PubMed, Embase, and Scopus were searched on November 18, 2022. Methodology followed the Arksey and O'Malley framework for scoping reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews guidelines. Two investigators independently screened abstracts and full-texts of citations identified related to drug dosing and SLED. Exclusion criteria included case reports, conference abstracts, pediatrics, treatment dialysis, and non-human subjects. A standardized data extraction sheet was used to collate and summarize data. The quality of evidence was evaluated by two investigators using the Mixed Methods Appraisal Tool. A total of 230 citations were identified for screening. Of these, 29 studies met criteria for inclusion after full-text review. Four drug groups including beta-lactam antibiotics, non-beta-lactam antibiotics, antifungals, and levetiracetam were identified. Dialysate rates, dialysis durations, and medication doses used varied widely across studies. Outcomes and pharmacokinetic parameters that were assessed were also heterogenous. Drug dosing in SLED is challenging and there is minimal evidence available to guide appropriate dosing. Larger studies are needed to more accurately determine how to appropriately dose medications in SLED. Therapeutic drug monitoring should be used in all patients on SLED when available.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"948-955"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865046","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":"Precision medicine to identify, prevent, and treat pediatric obesity.","authors":"Emma M Tillman, Selsbiel Mertami","doi":"10.1002/phar.4626","DOIUrl":"10.1002/phar.4626","url":null,"abstract":"<p><p>Pediatric obesity is a growing health concern that has many secondary adverse health implications. Personalized medicine is a tool that can be used to optimize diagnosis and treatments of many diseases. In this review, we will focus on three areas related to the genetics of pediatric obesity: (i) genetic causes predisposing to pediatric obesity, (ii) pharmacogenomics that may predict weight gain associated with pharmacotherapy, and (iii) pharmacogenomics of anti-obesity pharmacotherapy. This narrative review evaluates genetic cause of pediatric obesity and how genetic findings can be used to optimize pharmacotherapy to minimize weight gain and optimize obesity treatment in pediatric patients. Pediatric obesity has many genetic causes including genomic obesity syndromes and monogenic obesity disorders. Several genetic etiologies of obesity have current or emerging targeted genetic therapies. Pharmacogenomic (PGx) targets associated with pharmacotherapy-induced weight gain have been identified for antipsychotic, antiepileptic, antidepressant therapies, and steroids, yet to date no clinical guidelines exist for application use of PGx to tailor pharmacotherapy to avoid weight gain. As legislation evolves for genetic testing coverage and technology advances, this will decrease cost and expand access to genetic testing. This will result in identification of potential genetic causes of obesity and genes that predispose to pharmacotherapy-induced weight gain. Advances in precision medicine can ultimately lead to development of clinical practice guidelines on how to apply genetic findings to optimize pharmacotherapy to treat genetic targets of obesity and avoid weight gain as an adverse event associated with pharmacotherapy.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"939-947"},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644383","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}