Clinical Pharmacology & Therapeutics最新文献

{"title":"Risk of Infections with SGLT2 Inhibitors Versus DPP4 Inhibitors: A Population-Based Cohort Study Using Antibiotic Dispensing Data.","authors":"Maria J Alfonso Arvez, George S Q Tan, Sam Wade, Zanfina Ademi, Jenni Ilomäki, J Simon Bell","doi":"10.1002/cpt.70016","DOIUrl":"https://doi.org/10.1002/cpt.70016","url":null,"abstract":"<p><p>This study compared the number and cumulative dose of antibiotic dispensings among new users of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors following hospital discharge in individuals with type 2 diabetes. A retrospective cohort study was conducted using data from public and private hospitals in Victoria, Australia. Antibiotic dispensings were assessed over 12 months among new users of these medicines. Negative binomial regression with inverse probability of treatment weighting was applied to estimate weighted incidence rate ratios and confidence intervals for the total number of antibiotic dispensings and cumulative defined daily doses, stratified by antibiotic class. A total of 58.3% of SGLT2 inhibitor users (9,162 individuals) and 61.4% of DPP4 inhibitor users (16,589 individuals) received antibiotics. Initiators of SGLT2 inhibitors had a lower number of overall antibiotic dispensings compared with initiators of DPP4 inhibitors (weighted incidence rate ratio 0.88, 95% confidence interval 0.85 to 0.90), a pattern that was consistent across antibiotic classes. SGLT2 inhibitor initiators also had lower cumulative defined daily doses overall (weighted incidence rate ratio 0.89, 95% confidence interval 0.86 to 0.93), with significantly lower doses for penicillins, sulphonamides, and quinolones. These findings suggest that the initiation of SGLT2 inhibitors was associated with lower antibiotic use in terms of both the number of dispensings and cumulative dose, indicating potentially lower rates of infections among individuals with type 2 diabetes.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytochrome P450 2D6 *17 and *29 Allele Activity for Risperidone Metabolism: Advancing Precision Medicine Health Equity.","authors":"Oyinlade Kehinde, Samuel E Vaughn, Ogochukwu Amaeze, Paul Toren, Brandon Retke, Akinyemi Oni-Orisan, Laura B Ramsey","doi":"10.1002/cpt.70012","DOIUrl":"https://doi.org/10.1002/cpt.70012","url":null,"abstract":"<p><p>CYP2D6 alleles with low frequency in Eurocentrically biased study populations are often excluded from pharmacogenetic investigation and consequently may have misassigned activity values. This health inequity may be contributing to imprecise dose predictions for CYP2D6-metabolizing drugs. The objective of this study was to determine how sub-Saharan African-specific CYP2D6*17 and *29 alleles affect risperidone metabolism. To do this, we generated the largest real-world cohort of risperidone users in an African study population for pharmacogenetic studies. Risperidone users ≤ 18 years old were recruited from the Federal Neuro-Psychiatric Hospital. Health records were obtained by parent report and paper charts. CYP2D6 genotyping was performed for > 20 variants. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined by liquid chromatography mass spectrometry. CYP2D6 activity was calculated based on the metabolic ratio 9-hydroxyrisperidone:risperidone. Multivariable linear regression modeling was performed to determine the association between our alleles of interest and log-transformed ratio-defined CYP2D6 activity relative to star alleles with established activity values. Across 208 enrolled participants, CYP2D6 activity value for *17 was found to be twice that of normal function alleles, while *29 was comparable to no function alleles. These results contrast previous values assigned to *17 and *29 from guidelines, which are not based on evidence with risperidone, suggesting the possibility of substrate specificity for these alleles. Ultimately, our findings have the potential to improve risperidone prescribing, especially for patient groups with substantial sub-Saharan African ancestry. Importantly, this work underscores the critical need to better understand the effects of ancestry-specific alleles for achieving equitable pharmacotherapeutic health outcomes.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Hepatic Impairment Dosing in FDA Approvals Between 2002 and 2024.","authors":"Deandra A Cassel, Gilbert J Burckart, Martina D Sahre, Gelareh A Abulwerdi","doi":"10.1002/cpt.70011","DOIUrl":"https://doi.org/10.1002/cpt.70011","url":null,"abstract":"<p><p>The safety and efficacy of drugs metabolized by the liver can be substantially impacted by alterations in hepatic function. However, hepatic impairment (HI) is rarely evaluated in pediatric drug development due to challenges such as the relatively small number of patients, differences in adult and pediatric liver disease, and the lack of agreed-upon markers to assess HI severity. The objectives of the study were to (1) examine adult and pediatric HI dosing recommendations in US FDA prescribing information (PI) and pediatric dosing handbooks, Lexicomp and Micromedex, and (2) identify the clinical evidence behind HI dosing recommendations for pediatric patients. A total of 61 drugs containing both a pediatric indication and the word \"hepatic\" in the Dosage and Administration section of the PI were reviewed. Of the 61 drugs, only eight drugs included pediatric-specific HI dosing recommendations, with seven based on the Child-Pugh classification. Pharmacokinetic studies in adults with HI were the primary evidence behind the recommendations for all eight drugs, and only one drug was evaluated in pediatric patients with mild HI. Lexicomp and Micromedex provided consistent HI dosing recommendations with the PI and did not cite additional evidence. Overall, there is a gap in dosing recommendations for pediatric patients with HI. Alternative approaches, such as modeling and simulation based on drug- and disease-specific parameters, may help address knowledge gaps for pediatric patients with HI in the future.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recommended Phase II Doses of Talquetamab in Patients With Relapsed/Refractory Multiple Myeloma From MonumenTAL-1: Clinical Pharmacology Results","authors":"Jue Gong,&nbsp;Jie Zhou,&nbsp;Dongfen Yuan,&nbsp;Xuewen Ma,&nbsp;Deeksha Vishwamitra,&nbsp;Brandi Hilder,&nbsp;Tara J. Masterson,&nbsp;Jaszianne Tolbert,&nbsp;Thomas Renaud,&nbsp;Christoph Heuck,&nbsp;Colleen Kane,&nbsp;Mahesh N. Samtani,&nbsp;Suzette Girgis,&nbsp;Nahor Haddish-Berhane,&nbsp;Jesus Berdeja,&nbsp;Amrita Krishnan,&nbsp;Daniele Ouellet","doi":"10.1002/cpt.70004","DOIUrl":"10.1002/cpt.70004","url":null,"abstract":"<p>Talquetamab is the first and only GPRC5D × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). In the phase I/II MonumenTAL-1 study, overall response rates (ORRs) were &gt; 66% in patients with RRMM treated with subcutaneous talquetamab at the recommended phase II doses (RP2Ds): 0.4 mg/kg weekly and 0.8 mg/kg every other week. We characterized the pharmacokinetics (PK), pharmacodynamics, immunogenicity, and exposure-response relationships for efficacy and safety following talquetamab administration in phase I and II. In phase I, talquetamab exposure increased in an approximately dose-proportional manner across intravenous and subcutaneous doses and was maintained around or above the 90% maximum effective concentration identified in an ex vivo cytotoxic assay at the RP2Ds. Higher levels of T-cell activation and cytokine induction were observed at the RP2Ds compared with lower doses. Talquetamab demonstrated time-dependent clearance with a half-life of 7.56 days at initial treatment and 12.2 days at steady state. Patients with immunoglobulin G multiple myeloma and International Staging System (ISS) stage II/III exhibited higher clearance of talquetamab, which resulted in lower exposure. Dose adjustment based on myeloma subtype and ISS stage was not required. In exposure-response analyses, a near-flat relationship was demonstrated for ORR, duration of response, and progression-free survival at the exposure range of the RP2Ds. In safety exposure-response analyses, rates of grade 1/2 dysgeusia increased with higher exposures. The incidence of anti-talquetamab antibodies had no apparent impact on the PK, efficacy, or safety of talquetamab. These clinical pharmacology results support the selection of the talquetamab RP2Ds.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"118 4","pages":"954-966"},"PeriodicalIF":5.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Early Clinical Trials: The Transformative Potential of Decentralized Designs and Digital Technologies in Phase 1 Clinical Trial.","authors":"Bimal K Malhotra, Josué Kunjom Mfopou, Isabelle Huyghe, Pascal Ryckmans, Nathalie Severs, Anna Plotka, Kim-Claire Tabner, Malgorzata Anna Jennes, Anand Bhuvanendran Nair, Anna Colzi","doi":"10.1002/cpt.70002","DOIUrl":"https://doi.org/10.1002/cpt.70002","url":null,"abstract":"<p><p>A Phase 1, open-label, single-dose, fixed-sequence crossover study utilizing a hybrid decentralized clinical trial (DCT) design with and without practice sessions for wearable devices and PK sampling was conducted in eight healthy participants. Using etrasimod, the study assessed the feasibility of conducting a Phase 1 hybrid DCT by the Pfizer Clinical Research Unit (PCRU) staff, involving remote collection of pharmacokinetic (PK), safety, and tolerability data. The study objectives were to determine the PK and to assess the safety and tolerability of etrasimod clinical immediate release tablets in healthy adult participants in a hybrid DCT design. The study consisted of two periods, and the treatments were administered to participants in a fixed sequence: a single oral dose of etrasimod, then DCT with practice sessions in Period 1, followed by a single oral dose of etrasimod and DCT without practice sessions in Period 2. PK results were compared between Periods 1 and 2, and vs. PK from a single oral dose of etrasimod administered on site in a previous conventional design study. Serum etrasimod exposure was similar for non-practice vs. practice sessions within the hybrid DCT framework. PK parameters data from self-collected microsamples in the hybrid DCT design were comparable to PK parameters data from venous samples collected in a conventional setting. The wearable monitoring devices for recording the electrocardiogram (ECG) and vital parameters allowed remote and real-time assessment of safety and tolerability. Therefore, the study results demonstrated the feasibility of using multiple DCT modalities in Phase 1 trials for remote PK, safety, and tolerability assessments.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAB19, SERPINB9P1, and Pancreatitis in Patients Taking Azathioprine in Routine Clinical Practice: Genome and Transcriptome-Wide Association Studies","authors":"Shailja C. Shah,&nbsp;Tyler S. Reese,&nbsp;Laura L. Daniel,&nbsp;Jacy Zanussi,&nbsp;Alyson L. Dickson,&nbsp;Puran Nepal,&nbsp;Ran Tao,&nbsp;Tyne Miller-Fleming,&nbsp;Peter Straub,&nbsp;Jennifer Maizel,&nbsp;Adriana M. Hung,&nbsp;Wei-Qi Wei,&nbsp;Elizabeth J. Phillips,&nbsp;Nancy J. Cox,&nbsp;C. Michael Stein,&nbsp;QiPing Feng,&nbsp;Cecilia P. Chung","doi":"10.1002/cpt.70003","DOIUrl":"10.1002/cpt.70003","url":null,"abstract":"<p>Azathioprine is used to treat several inflammatory and autoimmune diseases. However, its use is limited by serious adverse events, including acute pancreatitis. Prior studies have found an association between the <i>HLA</i> region and thiopurine-induced acute pancreatitis (TIAP); however, in clinical practice, many patients with pancreatitis do not meet this strict criterion. We aimed to identify additional genes associated with azathioprine-related pancreatitis using genome-wide and transcriptome-wide association studies (GWAS and TWAS) by broadening the definition of pancreatitis. We conducted a retrospective study of azathioprine users with inflammatory conditions. We used electronic health records linked to genomic data from BioVU (Vanderbilt's biobank) and replicated the results using NIH's <i>All of Us</i>. The primary outcome was acute pancreatitis, and the secondary outcome was pancreatic injury. Sixteen patients with pancreatitis and 2085 control subjects were included from BioVU; the <i>All of Us</i> cohort included &lt; 20 patients with pancreatitis and 847 control subjects. The GWAS analysis (adjusted for 10 principal components of genetic ancestry, sex, age, and azathioprine indication) in the BioVU cohort found an association between pancreatic injury and rs2948386 in <i>RAB19</i> (OR = 3.47, <i>P</i> = 1.46E⁻⁸), which was replicated in <i>All of Us</i> (OR = 2.70, <i>P</i> = 4.18E⁻³). We also conducted a TWAS adjusting for the same factors above and found a significant association between genetically predicted pancreatic expression of <i>SERPINB9P1</i> with pancreatic injury (BioVU: effect size = 0.42, <i>P</i> = 1.48E-5; <i>All of Us</i>: effect size = 0.48, <i>P</i>-value = 0.01). In summary, we identified two new genetic associations for azathioprine-related pancreatic injury: the predicted expression of <i>SERPINB9P1</i> and a SNP in <i>RAB19</i>.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":"118 4","pages":"946-953"},"PeriodicalIF":5.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statistical Methods to Adjust for Treatment Switching in Real-World Clinical Studies: A Scoping Review and Descriptive Comparison.","authors":"Romain Jonathan Collet, Ângela Jornada Ben, Anita Natalia Varga, Frank van Leth, Mohamed El Alili, Jonas Esser, Judith Ekkina Bosmans, Johanna Maria van Dongen","doi":"10.1002/cpt.70013","DOIUrl":"https://doi.org/10.1002/cpt.70013","url":null,"abstract":"<p><p>Real-world data from sources, such as patient registries and electronic health records, can complement randomized controlled trials by providing timely, generalizable insights that better reflect routine clinical practice. However, the absence of randomization can introduce bias, particularly when treatment switching-defined as deviation from or discontinuation of the initial treatment-is influenced by time-varying confounders, that is, variables that are associated with both treatment decisions and outcomes over time. This study presents a comprehensive overview of statistical methods used to adjust for treatment switching in real-world studies to improve causal inference. We systematically searched MEDLINE and Embase for studies comparing at least two statistical methods for adjusting for treatment switching, from inception to December 2024. Forty-five studies were included, identifying four main categories of methods: (1) traditional approaches (intention-to-treat, per-protocol, as-treated, repeated measures); (2) propensity score-based methods (adjustment, matching, marginal structural models); (3) g-methods other than marginal structural models (g-computation, structural nested models, longitudinal targeted maximum likelihood estimation); (4) methods addressing unmeasured confounding (regression calibration, instrumental variables). Traditional methods are straightforward, but often yield biased estimates in the presence of treatment switching. Advanced methods, such as g-methods, are designed to adjust for time-varying confounding and can produce less biased estimates, though they require complex modeling. Instrumental variables and regression calibration relax the assumption of no unmeasured confounding, but rely on strong, often untestable conditions. By evaluating each method's assumptions, strengths, and limitations, we support applied researchers in selecting appropriate methods to strengthen causal inference in real-world studies.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling a Neo-Antigen-Driven Immune Response in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Study of the KLH Challenge Model.","authors":"Micha N Ronner, Hendrika W Grievink, Mahdi Saghari, Michelle Osse, Thierry P P van den Bosch, Jeffrey Damman, Marieke L de Kam, Jacobus Burggraaf, Naomi B Klarenbeek, Manon A A Jansen, Matthijs Moerland","doi":"10.1002/cpt.70007","DOIUrl":"https://doi.org/10.1002/cpt.70007","url":null,"abstract":"<p><p>Novel compounds targeting the adaptive immune system are commonly initially investigated in healthy volunteers (HV). HV frequently lack constitutively expressed drug-target engagement biomarkers, complicating the evaluation of pharmacological activity. The keyhole limpet hemocyanin (KLH) neo-antigen challenge elicits a controlled immune response in HV and is a potential model for investigating compounds targeting the adaptive immune system. A randomized, double-blind, placebo-controlled study in HV was conducted, investigating the effects of repeated immunizations with KLH on Days 1, 15, and 29, followed by intradermal KLH administration on Day 50. Systemically, KLH-specific antibodies were evaluated. Leukocytes were stimulated ex vivo to determine KLH-specific responses using ELISpot. Locally, KLH skin response was evaluated 0-48 hours post intradermal administration, using imaging, suction blister fluid analysis, and biopsy analysis. Twelve male HV aged 18-42 years completed the study. KLH antibody levels increased incrementally. ELISpot analyses demonstrated KLH-specific IFN-γ and IL-13 responses. Intradermal KLH injection drove a peak response 24 h after administration, observed as erythema and increased perfusion. Blister fluid analysis showed cell influx (T cells; B cells; monocytes; dendritic cells) at 24 h, largely decreasing at 48 h, as confirmed by immunofluorescent staining of skin biopsies. These findings demonstrate a T-cell-mediated response to intradermal KLH that is more rapid than the classical delayed-type hypersensitivity response. This study highlights the importance of the timing of measurements and combining non-invasive and invasive biomarkers. The KLH neo-antigen challenge model presented in this study offers a framework to study the effect of novel immunomodulatory compounds on the adaptive immune system early in clinical development.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimizing Racial Algorithmic Bias when Predicting Electronic Health Record Data Completeness.","authors":"Priyanka Anand, Yinzhu Jin, Jun Liu, Joyce Lii, Shruti Belitkar, Kueiyu Joshua Lin","doi":"10.1002/cpt.3758","DOIUrl":"https://doi.org/10.1002/cpt.3758","url":null,"abstract":"<p><p>The previously developed algorithm for identifying subjects with high electronic health record (EHR)-continuity performed suboptimally in racially diverse populations. We aimed to improve the performance by optimizing the race modeling strategy. We randomly divided TriNetX claims-linked EHR dataset from 11 US-based healthcare organizations into training (70%) and testing data (30%) to develop and test models with and without race interactions and race-specific models. We held out a Medicaid-linked EHR dataset as validation data. Study subjects were ≥18 years with ≥365 days of continuous insurance enrollment overlapping an EHR encounter. We used cross-validated least absolute shrinkage and selection operator (LASSO) to select predictors of high EHR-continuity. We compared the model performance using area under receiver operating curve (AUC). There were 550,859, 236,089, and 65,956 subjects in the training, testing, and validation datasets, respectively. In the validation set, the introduction of race-interaction terms resulted in improved model performance in Black (AUC 0.821 vs. 0.812, P < 0.001) and other non-White race (AUC 0.828 vs. 0.812, P < 0.001) subgroups. The performance of the race-specific models did not differ substantially from that of the models with race-interaction terms in the race subgroups. Using the race interactions model, subjects in the top 50% of predicted EHR-continuity had 2-3-fold lesser misclassification of 40 comparative effectiveness research (CER) relevant variables. The inclusion of race-interaction terms improved model performance in the race subgroups. Using the EHR-continuity prediction algorithm with race-interaction terms can potentially reduce algorithmic bias for racial minorities.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights Into Patient-Level Exposure to Actionable Pharmacogenomic Medications in Australia Using a New National Pharmacogenomic Guideline.","authors":"Bella D Ianni, Chin Hang Yiu, Mohammad A Ali, Christine Y Lu","doi":"10.1002/cpt.70006","DOIUrl":"https://doi.org/10.1002/cpt.70006","url":null,"abstract":"<p><p>This study assessed the use of 35 pharmacogenomic (PGx) medications listed in the Royal College of Pathologists of Australasia (RCPA) guideline, estimated the potential costs of subsidizing PGx testing in Australia, and predicted related prescribing changes. Using administrative claims data from the Pharmaceutical Benefits Scheme, accessed via the Australian Bureau of Statistics DataLab, we identified individuals who received any of the 35 medications between January 2021 and December 2023. Incident prescribing rates were calculated for children (0-17), adults (18-64), and older adults (65+). Adults (14.91%) and older adults (14.44%) had the highest rates of PGx medication use, followed by children (3.53%). Commonly prescribed medications included proton pump inhibitors, with frequent associations to genes such as CYP2C19 across all age groups. Estimated costs of PGx testing, assuming 50% and 75% population uptake, were highest for older adults: AUD$1.95 million and AUD$2.93 million, respectively. Predicted prescribing changes, based on literature-reported phenotype frequencies by ancestry, suggested that up to 18.58% of individuals using drugs like clopidogrel or voriconazole may need alternative treatments due to poor metabolism. These findings highlight the clinical potential of integrating PGx testing into routine practice, especially for medications included in international pharmacogenomic guidelines. While implementation would entail significant upfront costs, PGx testing could enhance medication safety and effectiveness and health care cost-efficiency. Future research should focus on scalable strategies for PGx implementation across diverse health care settings to optimize patient care globally.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}