Clinical Drug Investigation最新文献

{"title":"Effect of Food on the Pharmacokinetic Characteristics of a Single Oral Dose of D-1553, a Selective Inhibitor of KRAS^G12C, in Healthy Chinese Subjects.","authors":"Yue Liu, Xin Gao, Yang Li, Xuemei He, Zhe Shi, Ling Zhang, Yaolin Wang, Aixin Shi","doi":"10.1007/s40261-025-01430-1","DOIUrl":"10.1007/s40261-025-01430-1","url":null,"abstract":"<p><strong>Background and objective: </strong>D-1553 (garsorasib) is a novel and selective oral KRAS^G12C inhibitor. This study aims to evaluate the effect of food on the single-dose pharmacokinetics (PK) of D-1553 tablet in healthy Chinese subjects. Also the safety and tolerability of single-dose D-1553 in subjects are also evaluated.</p><p><strong>Methods: </strong>A randomized, open-label, single-dose, two-intervention (fed vs fasting), two-period, two-sequence crossover study was performed on 14 healthy Chinese subjects. Plasma concentrations of D-1553 were determined by the liquid chromatography-tandem mass spectrometry method. Safety evaluations were carried out during the study period. The main PK parameters of the two formulations of D-1553 were calculated by non-compartmental analysis using Phoenix WinNonlin (Version 8.3) software.</p><p><strong>Results: </strong>The geometric mean ratios (90% confidence interval [CI]) of AUC_0-t and AUC_0-∞ in the high-fat meal condition versus the fasting condition were 86.19% (78.30%, 94.87%) and 83.30% (75.77%, 91.58%), respectively. The geometric mean ratio (90% CI) of C_max values in high-fat meal condition to that observed in fasting condition were 109.74% (100.22%,120.15%). The p value of T_max was 0.1484 (fed vs fasting). Two subjects (14.3%) reported 4 treatment-emergent adverse events (TEAEs) in the fasting condition, and no subjects reported TEAEs in the fed condition. All adverse reactions were mild and had recovered by the end of the study.</p><p><strong>Conclusion: </strong>The study indicated that a high-calorie and high-fat meal has no clinically relevant impact on the PK and bioavailability of D-1553 in healthy Chinese subjects. D-1553 was generally safe and well-tolerated under both fasting and fed conditions. The findings suggest that D-1553 could be administered orally with or without food.</p><p><strong>Clinical trials: </strong>ClinicalTrials.gov Identifer CTR20212761; registered on 4 Nov 2021.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"201-206"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656278","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":"Guanfacine Use in the ICU for Management of Sedation Weaning.","authors":"Young R Lee, Alayna Garza, Laureen Kiama","doi":"10.1007/s40261-025-01434-x","DOIUrl":"10.1007/s40261-025-01434-x","url":null,"abstract":"<p><p>Recent evidence highlights the increasing utilization of guanfacine in the intensive care unit. While dexmedetomidine is a widely used sedative and anti-anxiety agent in the intensive care unit, prolonged use can lead to withdrawal effects when attempting to reduce the dosage. This has generated interest in using guanfacine to manage agitation in patients being weaned off dexmedetomidine. Clonidine has been used for dexmedetomidine weaning, but its use has been associated with adverse cardiovascular events. Some observational studies and case reports have explored the use of guanfacine and have shown its benefits and tolerability for patients taking dexmedetomidine experiencing adverse effects. Guanfacine is increasingly being used in the intensive care unit instead of clonidine and is commonly prescribed for the management of withdrawal effects. While there are limited data from observational studies, it holds promise for future clinical research and broader adoption of guanfacine in the intensive care unit.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"169-173"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613208","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 Cost Effectiveness of Adjunctive Medical Cannabis Therapy in the Treatment of Moderate Post-Traumatic Stress Disorder.","authors":"Mitchell L Doucette, Dipak Hemraj, D Luke Macfarlan, Junella Chin, Emily Fisher","doi":"10.1007/s40261-025-01424-z","DOIUrl":"10.1007/s40261-025-01424-z","url":null,"abstract":"<p><strong>Introduction: </strong>Research on the benefits of medical cannabis (MC) is emerging and supports its use as a treatment for post-traumatic stress disorder (PTSD). This study aimed to evaluate the cost effectiveness of MC as an adjunctive therapy for moderate PTSD under varying reimbursement scenarios.</p><p><strong>Methods: </strong>A cost-utility analysis was conducted from the US payor perspective, using pricing data from the largest multi-state MC producer and established literature on standard PTSD treatments. We analyzed eight MC product types: dried flower, oral solutions, tablets, and edibles, each available in low/moderate (LM) and high-cost formulations. Incremental cost-utility ratios (ICURs) were calculated for these products across reimbursement levels of 100%, 75%, 50%, and 25%. Probabilistic sensitivity analyses with 10,000 Monte Carlo simulations were conducted to assess cost-effectiveness acceptability across willingness-to-pay (WTP) thresholds of $0-$100,000 per quality-adjusted life year (QALY) gained.</p><p><strong>Results: </strong>Non-flower MC products (edibles, oral solutions, and tablets) consistently demonstrated cost-effectiveness under a WTP threshold of $50,000, even at 100% reimbursement. Dried flower products, while less cost effective due to higher costs, achieved cost effectiveness under 75% or lower reimbursement levels for LM cost formulations. Sensitivity analyses confirmed robust ICURs for non-flower products, with narrower variability compared to dried flower products.</p><p><strong>Conclusions: </strong>Medical cannabis products, particularly non-flower formulations, represent a cost-effective adjunctive therapy for moderate PTSD under various reimbursement scenarios. This analysis underscores the importance of evidence-based reimbursement policies to improve patient access to cost-effective treatments while ensuring financial sustainability for payors.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"207-220"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491197","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":"Frequency of Acute Kidney Injury After the Initiation of Vitamin D Receptor Activators: A Multicenter Retrospective Observational Study.","authors":"Masanori Nakanishi, Tomohiro Mizuno, Shinya Sakai, Daiki Hira, Takenao Koseki, Takeshi Matsubara, Hideki Yokoi, Motoko Yanagita, Tomohiro Terada, Shigeki Yamada, Naotake Tsuboi","doi":"10.1007/s40261-025-01429-8","DOIUrl":"10.1007/s40261-025-01429-8","url":null,"abstract":"<p><strong>Background and objectives: </strong>Vitamin D receptor activators (VDRAs) are widely used in patients with osteoporosis; however, the frequency of acute kidney injury (AKI) due to VDRAs is unclear. This study aimed to investigate whether the incidence of AKI after VDRA initiation differed among patients with different renal functions.</p><p><strong>Methods: </strong>The medical records of Japanese patients who were newly prescribed with VDRAs for osteoporosis at the Fujita Health University Hospital or Kyoto University Hospital between April 2012 and March 2022 were retrospectively reviewed in this study. The RIFLE (Risk, Injury, Failure, Loss of function, End-stage kidney disease) criteria were used to assess the incidence of AKI within 7 days after initiation of VDRA therapy. Additionally, the AKI algorithm was used to assess the incidence of AKI from 8 to 365 days after initiation of VDRA therapy.</p><p><strong>Results: </strong>The incidence of AKI, as defined by the RIFLE criteria, was significantly higher in patients with normal renal function or end-stage renal failure than in those with mild renal decline (p < 0.05); the incidence of AKI, defined using the AKI algorithm, showed a similar trend. We found that the lack of serum calcium level monitoring before the initiation of VDRAs might be a risk factor for AKI defined by the RIFLE criteria (odds ratio = 2.004, p = 0.096).</p><p><strong>Conclusions: </strong>The incidence of AKI after the initiation of VDRA therapy was high, even if renal function was normal. Thus, our results suggest that monitoring serum calcium levels before the initiation of VDRA therapy is necessary, regardless of renal function.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"191-199"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613770","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, Pharmacodynamics, and Safety Evaluation of the Novel HIF-PH Inhibitor Enarodustat: An Open-Label Phase I Study in Healthy Chinese Participants.","authors":"Cheng Cui, Xiaoye Niu, Haiyan Li, Ruijie Zhang, Lei Geng, Wei Lin, Zichen Liu, Xiaohong Wang, Dongyang Liu","doi":"10.1007/s40261-025-01428-9","DOIUrl":"10.1007/s40261-025-01428-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Enarodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor. We evaluated the pharmacokinetics, pharmacodynamics, and safety profile of domestic enarodustat (SAL-0951) and analyzed the influence of ethnic factors.</p><p><strong>Methods: </strong>In this phase I study, healthy Chinese participants received single and multiple oral doses (1, 5, and 15 mg) of SAL-0951 while in a fasted state. We monitored the pharmacokinetics, pharmacodynamics, and safety characteristics and analyzed the impact of ethnicity on pharmacokinetic characteristics.</p><p><strong>Results: </strong>In total, 33 healthy Chinese participants were enrolled; the mean age was 31.2 ± a standard deviation of 5.5 years. After single doses of 1, 5, and 15 mg were administered under fasted conditions, SAL-0951 was rapidly absorbed. Mean maximum plasma concentration and area under the plasma concentration-time curve from time 0 to the last quantifiable concentration increased dose proportionately from 0.14 to 2.54 μg/mL and from 0.63 to 9.50 h × μg/mL, respectively. The elimination half-life was 6.13, 6.32, and 6.74 h, respectively, in these three groups, and the mean value of apparent clearance ranged from 1.64 to 1.89 L/h. SAL-0951 was excreted mostly as the parent compound. It reached a stable concentration after 5 days of multiple-dose administration. We observed no drug accumulation or time-dependent pharmacokinetic characteristics and no significant difference in pharmacokinetic characteristics between Chinese and Japanese participants.</p><p><strong>Conclusion: </strong>SAL-0951 was safe and well tolerated in healthy Chinese participants and had a linear pharmacokinetic profile. We found no ethnic differences in the pharmacokinetic characteristics of the drug between Chinese and Japanese populations.</p><p><strong>Clinical trial registration: </strong>Registered at Chinadrugtrials.org.cn, registration number CTR2020245.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"179-189"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613276","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":"Tebentafusp Versus Nivolumab Plus Ipilimumab for Metastatic Uveal Melanoma: An E-Value Sensitivity Analysis Assessing Effect of Unmeasured Confounders on Observational Associations.","authors":"Na Zhang, Yu-Wei Qiao, Dan Su, Guo Yu, Guo-Fu Li","doi":"10.1007/s40261-025-01422-1","DOIUrl":"10.1007/s40261-025-01422-1","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"165-168"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440022","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":"Age-Specific Plasma Concentration, Efficacy and Safety of Ciprofol (Cipepofol) for Induction and Maintenance of General Anesthesia in Pediatric Patients Undergoing Elective Surgery: A Single-Arm Prospective, Pragmatic Trial.","authors":"Zheng Chen, Tuochao Peng, Shuibing Zhang, Qiaoyun Yang, Shuangquan Qu, Yong Cao, Junxia Chen, Yiwei Mao","doi":"10.1007/s40261-025-01425-y","DOIUrl":"10.1007/s40261-025-01425-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Ciprofol (Cipepofol) currently has well-established clinical research data in adult Chinese patients, but there is a lack of reliable research data in pediatric patients. This study aimed to assess the age-specific plasma concentration, efficacy and safety profiles of cipepofol in pediatric patients aged 2-17 years during the induction and maintenance of general anesthesia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a single-arm, open-label, prospective, pragmatic study conducted in the Hunan Children's Hospital from May 10, 2023 to August 25, 2023, that involved pediatric patients undergoing elective surgery after the induction and maintenance of general anesthesia. Cipepofol was administered as an intravenous bolus injection of 0.6 mg/kg (patients aged 2-11 years) or 0.5 mg/kg (12-17 years) for induction, followed by an initial maintenance infusion of 1.2 mg/kg/h or 1.4 mg/kg/h, respectively. The primary endpoint-plasma concentration of cipepofol was measured using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The age-specific plasma concentration, efficacy and safety profiles of cipepofol are summarized using descriptive statistics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All 38 enrolled patients completed the study, including 14 children aged 2-5 years, 12 children aged 6-11 years and 12 children aged 12-17 years. The trends of plasma concentration variations among patients in the three age groups were largely consistent. The success rates of anesthesia induction and maintenance for patients in the three groups were both 100%, and no patients required rescue medication. Children aged 2 to 5 years had the longest median durations of successful anesthetic induction (1.1 min) and eyelash reflection disappearance (1.2 min), while the median durations for patients aged 6-11 years and those aged 12-17 years (0.5 and 0.5 min) were similar. The median time to extubation and length of stay in the post-anesthesia care unit tended to be the longest in children aged 6-11 years (23.5 and 30.0 min) but were comparable for those aged 2-5 years (10.5 min and 20.0 min) and 12-17 years (11.0 and 20.0 min). The median time to full alertness tended to decrease with increasing age (33.7 vs 25.8 vs 22.7 min). A total of 4 (10.5%) patients experienced treatment-emergent adverse events in those aged 2-5 years or 12-17 years, with a severity of grade 1 or grade 2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Cipepofol had good safety for the induction and maintenance of general anesthesia in pediatric patients aged over 2 years. The dosing regimen with an intravenous bolus injection of 0.5 mg/kg for induction, followed by an initial maintenance infusion of 1.4 mg/kg/h was adequate for children aged 12-17 years; age-specific dose regimen for children aged 2-11 years should be improved by further large-scale prospective studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;ChiCTR2400085640, July","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"137-150"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439952","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":"Economic Model of Uridine Triacetate Versus Supportive Care for the Treatment of Patients with Life-Threatening Early-Onset Severe Toxicity.","authors":"Jorge J Garcia, Alice Beers, Paige Reid, Salvatore Miragliotta, Suzanne Ward, Setareh A Williams, Michelle Barnard, Megan Bourque, Chantal Trepanier, Amanda Griffin","doi":"10.1007/s40261-025-01426-x","DOIUrl":"10.1007/s40261-025-01426-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Early-onset severe toxicity following the administration of 5-fluorouracil (5-FU) or capecitabine occurs in approximately 10-30% of patients receiving fluoropyrimidine therapy in the USA and is fatal to at least 0.5% of patients treated. Supportive care measures used to manage symptoms of toxicity are associated with extended hospital length of stay, high cost of care, and poor survival. Uridine triacetate is indicated as an emergency treatment for patients who exhibit early-onset, severe or life-threatening toxicity, and has been shown to significantly improve clinical outcomes. Despite its life-saving capability to reverse early-onset severe toxicity, uridine triacetate may be underutilized.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This study aims to evaluate the economic impact of uridine triacetate as a rescue therapy for adult patients from the US hospital payer perspective for early-onset severe toxicity, who are expected to die without treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A decision tree model was developed to compare inpatient survival, hospital length of stay, and inpatient healthcare resource utilization for patients treated with and without uridine triacetate. Costs associated with hospitalization, including supportive care measures and monitoring were evaluated, considering medications and procedures commonly used to manage various severe toxicities experienced (e.g., gastrointestinal, hematological, etc.). The model compared the hypothetical current practice, in which approximately half of patients expected to die from early-onset severe toxicity receive uridine triacetate in addition to supportive care, with the proposed future practice in which all eligible patients receive uridine triacetate during their hospital stay. Hypothetical practical scenarios for US institutions were also considered.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;For each adult patient hospitalized for early-onset severe or life-threatening toxicity who would be expected to die without treatment, adoption of uridine triacetate as a rescue treatment was associated with clinical benefits, including increased inpatient survival (48.5%) and a 7.3-day reduction in total hospital length of stay per patient. Treatment of each additional patient with uridine triacetate was associated with an incremental cost of US$25,247 per patient. Seventy percent of the drug cost was offset by reduction in inpatient healthcare resources utilization. This cost offset is likely underestimated as it does not include additional savings from potential reimbursements associated with changes in hospital length of stay, readmissions and discounting. Hypothetical scenarios demonstrated that model outputs were most sensitive to changes in length of stay and hospitalization costs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Optimal treatment with uridine triacetate for all hospitalized patients in the USA expected to die from early-onset severe toxicity has the potential to improve ","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"111-123"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476333","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":"Dose-Dependent Relationship Between Long-Term Metformin Use and the Risk of Diabetic Retinopathy: A Population-Based Cohort Study.","authors":"Yu-Ching Li, Kuang-Hua Huang, Yih Yang, Shuo-Yan Gau, Tung-Han Tsai, Chien-Ying Lee","doi":"10.1007/s40261-025-01421-2","DOIUrl":"10.1007/s40261-025-01421-2","url":null,"abstract":"<p><strong>Background and objective: </strong>Recent research has raised concerns about the association between metformin treatment in patients with diabetes mellitus (DM) and an increased risk of diabetic retinopathy. We sought to investigate this relationship, specifically examining if metformin use affects diabetic retinopathy risk in a dose-dependent manner.</p><p><strong>Methods: </strong>This study was a secondary data analysis based on a nationwide population database in Taiwan. Patients with new-onset DM, an age of 20 years or older, and a diagnosis of type 2 DM received at any time during 2002-2013 were included in the study. Patients diagnosed with new-onset type 2 DM between 2002 and 2013 were enrolled as the study population. We divided them into two groups: those treated with metformin and those treated with sulfonylureas. A Cox proportional hazards model was employed to estimate the risk of diabetic retinopathy after 5 years of follow-up, including cumulative defined daily dose and intensity of metformin treatment.</p><p><strong>Results: </strong>A total of 241,231 patients received treatment with metformin, while 152,617 patients were treated with sulfonylureas. Compared with patients treated with sulfonylureas, patients who received metformin treatment, at a cumulative defined daily dose < 30, had a lower risk of diabetic retinopathy (adjusted hazard ratio = 0.77; 95% confidence interval 0.60-0.98). However, those with varying defined daily doses, especially at a higher metformin treatment level (> 25 defined daily dose), had a 2.43 times higher risk of diabetic retinopathy (95% confidence interval 1.37-4.30) compared with patients treated with sulfonylureas.</p><p><strong>Conclusions: </strong>Patients with DM treated with a lower cumulative dosage of metformin showed beneficial effects that were associated with a lower risk of diabetic retinopathy. In contrast, a higher intensity of metformin use had a greater risk of diabetic retinopathy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"125-136"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406078","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":"Dihydropyrimidine Dehydrogenase Deficiency (DPYD) Genotyping-Guided Fluoropyrimidine-Based Adjuvant Chemotherapy for Breast Cancer. A Cost-Effectiveness Analysis.","authors":"Dina Abushanab, Shaban Mohamed, Rania Abdel-Latif, Diala Alhaj Moustafa, Wafa Marridi, Shereen Elazzazy, Radja Badji, Wadha Al-Muftah, Said I Ismail, Salha Bujassoum, Asma Al-Thani, Daoud Al-Badriyeh, Moza Al Hail","doi":"10.1007/s40261-024-01413-8","DOIUrl":"10.1007/s40261-024-01413-8","url":null,"abstract":"<p><strong>Background and objective: </strong>While standard doses of adjuvant fluoropyrimidine-based chemotherapies are generally safe for most patients, the risk of severe adverse drug reactions (ADRs) is increased for those with dihydropyrimidine dehydrogenase deficiency (DPYD), a genetic variation that affects drug metabolism. The objective of this study was to examine the cost effectiveness of offering DPYD pharmacogenetic-guided care, where genetic testing informs personalized dosing versus the current standard of care (SoC), which involves administering fluoropyrimidine-based therapies without prior genetic screening, for local or metastatic breast cancer patients in Qatar.</p><p><strong>Methods: </strong>We developed a two-stage decision analysis, with an analytic tree model over a 6-month period, followed by a life-table Markov model over a lifetime horizon. We compared the current SoC with the alternate strategy of DPYD genetic screening in patients living in Qatar with local or metastatic breast cancer who were eligible for adjuvant fluoropyrimidine therapy. Clinical outcomes and utilities were obtained from published studies, while healthcare costs were estimated from Hamad Medical Corporation, Qatar. The short-term outcome included the incremental cost-effectiveness ratio (ICER), defined as cost per success (survival without grade III/IV ADRs) at 6 months. The long-term outcome was the ICER, defined as cost per quality-adjusted life year (QALY) gained, with a 3% annual discount rate. The study adopted a public healthcare perspective in Qatar. Sensitivity analyses were conducted to explore the impact of key input parameters on the robustness of the model.</p><p><strong>Results: </strong>In the short-term model, at its base case, DPYD genomic screening was dominant over SoC with a mean cost-saving of QAR84,585 (95% confidence interval [CI], 45,270-151,657). This cost saving reflects the overall economic benefits associated with the implementation of DPYD genomic screening. In the long-term model, compared to the current SoC, DPYD genetic screening would result in an ICER of QAR21,107 (95% CI -59,382-145,664) per QALY gained.</p><p><strong>Conclusion: </strong>Based on our model, implementing DPYD genetic screening to detect DPYD mutations in breast cancer patients before therapy initiation seems to be a cost-saving and cost-effective strategy in Qatar.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"151-163"},"PeriodicalIF":2.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064127","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}