Expert opinion on drug metabolism & toxicology最新文献_第2页

Drug-drug interactions potential with the HIV-1 capsid inhibitor lenacapavir. HIV-1囊壳抑制剂来那卡巴韦的潜在药物相互作用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-10-16 DOI: 10.1080/17425255.2024.2415295

Catia Marzolini, Sara Gibbons, Daniel Seddon, Saye Khoo

{"title":"Drug-drug interactions potential with the HIV-1 capsid inhibitor lenacapavir.","authors":"Catia Marzolini, Sara Gibbons, Daniel Seddon, Saye Khoo","doi":"10.1080/17425255.2024.2415295","DOIUrl":"10.1080/17425255.2024.2415295","url":null,"abstract":"Introduction: Lenacapavir is the first HIV-1 capsid inhibitor administered subcutaneously twice yearly. While lenacapavir is currently only indicated as salvage therapy, it has the potential to become a foundation of future treatments and to revolutionize HIV prevention.Areas covered: This review summarizes the pharmacology of lenacapavir with particular emphasis placed on its drug-drug interaction (DDI) potential as it is used in treatment-experienced individuals who often present multiple comorbidities and polypharmacy. The effect of lenacapavir on drug metabolizing enzymes and transporters as well as findings of DDI studies are summarized. These data were used to predict DDIs with 1073 comedications. Finally, the management of selected DDIs is discussed. Conferences/workshops abstracts (i.e. CROI, IAS, EACS, HIV Glasgow, PK workshop) were screened using the terms: 'lenacapavir,' 'capsid inhibitor,' 'GS-6207,' and a PubMed search was used to compile data until September 2024.Expert opinion: Lenacapavir has a favorable DDI profile with 80% of evaluated comedications estimated to have no clinically significant DDIs. More studies are needed to address pharmacological gaps including the pharmacokinetics of lenacapavir in special populations, its transfer across the blood-brain barrier or the placenta as well as the possibility to manage DDIs with moderate/strong inducers by reducing lenacapavir dosing interval.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"161-172"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The relationship between CYP2C9 gene polymorphisms and azilsartan metabolism in vitro. CYP2C9 基因多态性与阿齐沙坦体外代谢的关系

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-09-29 DOI: 10.1080/17425255.2024.2409255

Su-Su Bao, Peng-Fei Tang, Quan Zhou, Chuan-Feng Shao, Zhong-Xiang Xiao, Chen Cheng, Jian-Ping Cai, Yun-Lei Li

{"title":"The relationship between CYP2C9 gene polymorphisms and azilsartan metabolism in vitro.","authors":"Su-Su Bao, Peng-Fei Tang, Quan Zhou, Chuan-Feng Shao, Zhong-Xiang Xiao, Chen Cheng, Jian-Ping Cai, Yun-Lei Li","doi":"10.1080/17425255.2024.2409255","DOIUrl":"10.1080/17425255.2024.2409255","url":null,"abstract":"Background: The gene polymorphisms of the CYP2C9, as well as the substrate specificity of the enzyme, result in different clearances for different substrates by CYP2C9 variants.Research designand methods: The CYP2C9 wild type and 38 CYP2C9 variants, expressed in insectmicrosomes, were incubated with azilsartan. The resulting metabolite,O-desethyl azilsartan, was determined by HPLC-MS/MS. The enzyme kineticparameters of the 38 variants were calculated and compared with the wild type.Subsequently, we selected CYP2C9*1, *2, and *3 as target proteins for molecular docking with azilsartan to elucidate the mechanisms underlying changes in enzyme function.Results: Compared with CYP2C9*1, three variants (CYP2C9*29, *39, and *49) exhibited markedlyincreased CLint values (from 170%-275%, *p < 0.05), whereas 28 variants exhibited significantly decreased CLint values (from 3-63%,*p < 0.05). The molecular docking results showed that the binding energy of CYP2C9*2 and *3 was lower than that of the wild type.Conclusion: Thisassessment revealed the effect of CYP2C9 gene polymorphisms on azilsartan metabolism, establishing a theoretical basis for further in-vivo studies and clinical applications. This study will help expand the database of CYP2C9 gene-drug pairs and identify appropriate treatment strategies for azilsartan, contributing to the field of precision medicine.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"95-103"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Switching from cangrelor to oral P2Y₁₂ inhibitors: a focused review on drug-drug interactions. 从康格列洛转为口服 P2Y12 抑制剂：药物相互作用重点综述。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-10-20 DOI: 10.1080/17425255.2024.2418033

Giovanni Occhipinti, Luis Ortega-Paz, Francesco Franchi, Fabiana Rollini, Davide Capodanno, Salvatore Brugaletta, Dominick J Angiolillo

{"title":"Switching from cangrelor to oral P2Y12 inhibitors: a focused review on drug-drug interactions.","authors":"Giovanni Occhipinti, Luis Ortega-Paz, Francesco Franchi, Fabiana Rollini, Davide Capodanno, Salvatore Brugaletta, Dominick J Angiolillo","doi":"10.1080/17425255.2024.2418033","DOIUrl":"10.1080/17425255.2024.2418033","url":null,"abstract":"Introduction: Cangrelor, the only intravenous platelet P2Y12 receptor inhibitor, is characterized by a prompt and potent platelet inhibition, with a rapid offset of action. Large-scale clinical trials have shown that cangrelor reduce peri-procedural thrombotic events among patients undergoing percutaneous coronary interventions and not pre-treated with an oral P2Y12 receptor inhibitor. However, high P2Y12 receptor occupancy provided by cangrelor raises concerns for drug-drug interactions (DDIs) when transitioning to oral P2Y12 inhibitors.Areas covered: An understanding of the pharmacology of cangrelor and oral P2Y12 inhibitors is essential to define the optimal approach to transition to oral P2Y12 inhibitors without incurring the risk of DDIs. This review, based on a thorough literature search in major scientific databases (PubMed, Cochrane Library, Web of Science), synthesizes the pharmacology of cangrelor and the oral P2Y12 receptor inhibitors, providing the rationale for the occurrence of DDIs and strategies to avoid such risk.Expert opinion: The timing of transition from cangrelor to oral P2Y12 inhibitors plays a crucial role in the occurrence of DDIs, especially with clopidogrel and prasugrel. Currently, no evidence suggests a DDI when transitioning to ticagrelor. Adhering to product labels and guideline recommendations is crucial for optimizing safety and efficacy of cangrelor.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"29-40"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating the drug-drug interactions of SHR4640 on repaglinide and midazolam in healthy subjects. 评估 SHR4640 对健康受试者中瑞格列奈和咪达唑仑的药物相互作用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-14 DOI: 10.1080/17425255.2024.2428367

Yuanzhi Cheng, Xiaotong Hu, Zejun Pei, Zhe Zhang, Hongda Lin, Sheng Feng, Zhenyan Gao, Yanlin Ma, Zhihai Cao, Qian Zhang, Liang Zheng, Wei Zhang, Kai Shen, Wei Hu

{"title":"Evaluating the drug-drug interactions of SHR4640 on repaglinide and midazolam in healthy subjects.","authors":"Yuanzhi Cheng, Xiaotong Hu, Zejun Pei, Zhe Zhang, Hongda Lin, Sheng Feng, Zhenyan Gao, Yanlin Ma, Zhihai Cao, Qian Zhang, Liang Zheng, Wei Zhang, Kai Shen, Wei Hu","doi":"10.1080/17425255.2024.2428367","DOIUrl":"10.1080/17425255.2024.2428367","url":null,"abstract":"Background: SHR4640, a highly selective URAT1 inhibitor, was evaluated to investigate its inhibitory effects on CYP2C8 and CYP3A4 in vivo clinical trial. This study assessed the pharmacokinetic (PK) impact of SHR4640 when co-administered with the CYP2C8 probe substrate repaglinide and the CYP3A4 probe substrate midazolam.Research design and methods: In this single-center, randomized, double-blind, placebo-controlled study, participants were randomly allocated in a 1:1:1 ratio to SHR4640 Group A, SHR4640 Group B, and placebo group and received oral repaglinide, midazolam, SHR4640 or placebo at specific times. The primary endpoints included the main PK parameters of repaglinide and midazolam, both alone and in combination with SHR4640 (AUC0-inf, AUC0-t, and Cmax).Results: The increase in the area under the concentration-time curve (AUC) for repaglinide, when co-administered with SHR4640, was less than 1.25-fold, while the AUC for midazolam exhibited a slight increase of 46%.Conclusions: SHR4640 exerts a weak inhibitory effect on the AUC of CYP enzyme probe substrates and has minimal potential for drug-drug interactions and presents a favorable safety profile.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06196580 (Name: PK Effects of SHR4640 on Repaglinide and Midazolam, and the Impact of SHR4640 on QT Interval).","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"217-224"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug-drug interactions in HIV-infected patients receiving chemotherapy. 接受化疗的艾滋病毒感染者的药物相互作用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-09-24 DOI: 10.1080/17425255.2024.2408004

Chrystalyn Branch, Jan Parson-Martinez, Theodore James Cory

{"title":"Drug-drug interactions in HIV-infected patients receiving chemotherapy.","authors":"Chrystalyn Branch, Jan Parson-Martinez, Theodore James Cory","doi":"10.1080/17425255.2024.2408004","DOIUrl":"10.1080/17425255.2024.2408004","url":null,"abstract":"Introduction: Coadministration of antiretrovirals and anti-cancer medications may present many complex clinical scenarios. This is characterized by the potential for drug-drug interactions (DDIs) and the challenges that arise in patient management. In this article, we investigate the potential for DDIs between antiretrovirals, including protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), integrase strand transfer inhibitors (INSTIs), and anti-cancer medications.Areas covered: PubMed, Google Scholar, and Clinicaltrials.gov were searched for relevant articles in April 2024. Our review highlights PIs and NNRTIs as particularly prone to DDIs with anticancer agents, with implications for efficacy and toxicity of concomitant cancer therapy. We explain the mechanisms for interactions, emphasizing the significance of pharmacokinetic effects and enzyme induction or inhibition. We discuss clinical challenges encountered in the management of patients receiving combined ART and cancer therapy regimens.Expert opinion: Data are lacking for potential DDIs between antiretroviral and anti-cancer agents. While some interactions are documented, others are theoretical and based on the pharmacokinetic properties of the medications. Awareness of these interactions, inter-collaborative care between healthcare providers, and standardized treatment guidelines are all crucial for achieving optimal treatment outcomes and ensuring the well-being of patients with HIV/AIDS and cancer comorbidities.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"15-27"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease. 钾竞争性胃酸阻滞剂治疗胃食管反流病的安全性。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-09-24 DOI: 10.1080/17425255.2024.2397433

Angela Tietto, Sofia Faggin, Carmelo Scarpignato, Edoardo Vincenzo Savarino, Maria Cecilia Giron

{"title":"Safety of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease.","authors":"Angela Tietto, Sofia Faggin, Carmelo Scarpignato, Edoardo Vincenzo Savarino, Maria Cecilia Giron","doi":"10.1080/17425255.2024.2397433","DOIUrl":"10.1080/17425255.2024.2397433","url":null,"abstract":"Introduction: Proton pump inhibitors (PPIs) are the first-line treatment for gastroesophageal reflux disease (GERD). However, due to their intrinsic limitations, there are still unmet clinical needs that have fostered the development of potassium-competitive acid blockers (P-CABs). Currently, four different drugs (vonoprazan, tegoprazan, fexuprazan, and keverprazan) are marketed in some Asian countries, whereas only vonoprazan and tegoprazan are available in Western countries (USA and Brazil or Mexico, respectively).Areas covered: This review summarizes the current knowledge on P-CABs acute and long-term safety in GERD treatment compared to that of PPIs. Full-text articles and abstracts were searched in PubMed.Expert opinion: P-CABs proved to address some of the unmet clinical needs in GERD, with a favorable risk-benefit ratio compared to conventional PPIs. Preclinical and clinical findings have highlighted P-CAB safety to be superimposable, to that of PPIs, in short-term treatments, although further studies are warranted to monitor their effects in long-term therapy. From an epidemiological point of view, the paucity of rigorous data for many variables (e.g. age, ethnicity, drug interactions, comorbidities, genetic polymorphisms, interindividual susceptibility, and gut dysbiosis) deserves a worldwide framework of continuous pre/post-marketing pharmacovigilance programs to reduce potential confounding factors and accurately link acute and chronic P-CAB therapy to adverse outcomes.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"53-68"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug dosing optimization in critically ill children under continuous renal replacement therapy: from basic concepts to the bedside model informed precision dosing. 对接受持续肾脏替代治疗的重症儿童进行药物剂量优化：从基本概念到床边精准用药模型。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-04 DOI: 10.1080/17425255.2024.2422875

Mehdi Oualha, Michael Thy, Naïm Bouazza, Sihem Benaboud, Agathe Béranger

{"title":"Drug dosing optimization in critically ill children under continuous renal replacement therapy: from basic concepts to the bedside model informed precision dosing.","authors":"Mehdi Oualha, Michael Thy, Naïm Bouazza, Sihem Benaboud, Agathe Béranger","doi":"10.1080/17425255.2024.2422875","DOIUrl":"10.1080/17425255.2024.2422875","url":null,"abstract":"Introduction: Optimizing drug dosage in critically ill children undergoing Continuous Renal Replacement Therapy (CRRT) is mandatory and challenging, given the many factors impacting pharmacokinetics and pharmacodynamics coupled with the vulnerability of this population.Areas covered: A good understanding of the mechanisms that determine drug elimination via the CRRT technique is useful to avoid prescription pitfalls, however limited by the high between and within subject variability. The developments of population pharmacokinetic and physiologically based pharmacokinetic models derived from in-vivo and in-vitro studies, are challenging, but remain the most appropriate tool to suggest adjusted dosage regimens for every patient, throughout treatment. We searched PubMed using the search string: 'pediatrics OR children' AN 'continuous renal replacement therapy' AND 'pharmacokinetics' AND 'model informed precision dosing' AND, 'physiologically based pharmacokinetics,' AND 'therapeutic drug monitoring' until January 2024, regardless of language or publication status.Expert opinion: Familiarizing the pediatric intensivists with the therapeutic drug monitoring and providing clinicians the individualized prescribing software such as Model Informed Precision Dosing would be a significant step forward. The clinical benefit for patients remains to be demonstrated.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"173-190"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of GST polymorphism with adverse drug reactions: an analysis across multiple drug categories. GST 多态性与药物不良反应的关系：对多种药物类别的分析。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-06 DOI: 10.1080/17425255.2024.2426616

Soukaina Ettoury, Sara Louati, Ibtissam Saad, Kaoutar Bentayebi, Oumaima Zarrik, Jamal Eddine Bourkadi, Lahcen Belyamani, Youssef Daali, Rachid Eljaoudi

{"title":"Association of GST polymorphism with adverse drug reactions: an analysis across multiple drug categories.","authors":"Soukaina Ettoury, Sara Louati, Ibtissam Saad, Kaoutar Bentayebi, Oumaima Zarrik, Jamal Eddine Bourkadi, Lahcen Belyamani, Youssef Daali, Rachid Eljaoudi","doi":"10.1080/17425255.2024.2426616","DOIUrl":"10.1080/17425255.2024.2426616","url":null,"abstract":"Introduction: Adverse drug reactions (ADRs) pose a significant challenge in clinical practice, impacting patient safety and treatment outcomes. Genetic variations in drug-metabolizing enzymes, particularly glutathione S-transferases (GSTs), have been implicated in modulating individual susceptibility to ADRs.Areas covered: This overview aims to explore the association between GSTs genetic polymorphisms and ADRs across diverse drug categories documented in current literature. Here we cover antiepileptic, immunosuppressive, chemotherapeutic agents, analgesics, antivirals, and antibiotics.Expert opinion: According to the existing literature, the association between genetic polymorphisms in GST theta (GSTT1), GST mu (GSTM1), and GST pi (GSTP1) and adverse drug reaction occurrence has been frequently reported. However, the strength of these associations varies considerably among studies, with some showing inconsistent or contradictory results, underscoring the need for further investigations.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"191-201"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetic evaluation of efanesoctocog alfa: breakthrough factor VIII therapy for hemophilia A. efanesoctocog alfa 的药代动力学评估：A 型血友病的突破性 VIII 因子疗法。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-10-04 DOI: 10.1080/17425255.2024.2409931

Koji Yada, Keiji Nogami

{"title":"Pharmacokinetic evaluation of efanesoctocog alfa: breakthrough factor VIII therapy for hemophilia A.","authors":"Koji Yada, Keiji Nogami","doi":"10.1080/17425255.2024.2409931","DOIUrl":"10.1080/17425255.2024.2409931","url":null,"abstract":"Introduction: Blood coagulation factor (F)VIII functions as a cofactor in the tenase complex responsible for phospholipid-dependent FIXa-mediated activation of FX in plasma. Congenital defect of FVIII causes severe bleeding disorder, hemophilia (H) A. Intravenous FVIII replacement therapy is the gold standard therapy in patients with HA (PwHA) but requirement for frequent dosing of FVIII owing to pharmacokinetics burdens PwHA a lot. Efanesoctocog alfa is a new class of recombinant FVIII and has the ability to overcome conceivable unmet needs in treatment for PwHA.Areas covered: Efanesoctocog alfa is a B domain-deleted single-chain fusion FVIII connected to the Fc-region of human immunoglobulin G1, D'D3-fragment of von Willebrand factor (VWF), and unstructured hydrophilic recombinant polypeptides (XTEN). Owing to its novel design, it can function independently of endogenous VWF and elicits 2 to 4 times longer half-life compared to other existing FVIII products. The prolonged half-life contributes to maintain high level of FVIII activity for most of the week and has led to excellent hemostatic effect by once-weekly administration in phase 3 clinical trials.Expert opinion: Efanesoctocog alfa with outstanding pharmacological properties, well tolerated in the clinical trials, is a promising FVIII therapy for PwHA. Future studies should include long-term safety, especially in previously untreated patients.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"5-14"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimizing drug therapy during pregnancy: a spotlight on population pharmacokinetic modeling. 优化孕期药物治疗：聚焦群体药代动力学模型。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1080/17425255.2024.2420195

Prerna Dodeja, Nupur Chaphekar, Steve N Caritis, Raman Venkataramanan

{"title":"Optimizing drug therapy during pregnancy: a spotlight on population pharmacokinetic modeling.","authors":"Prerna Dodeja, Nupur Chaphekar, Steve N Caritis, Raman Venkataramanan","doi":"10.1080/17425255.2024.2420195","DOIUrl":"10.1080/17425255.2024.2420195","url":null,"abstract":"Introduction: Optimizing drug therapy during pregnancy is crucial for ensuring the safety of mothers and babiesPhysiological changes that occur during pregnancy can significantly alter the pharmacokinetics of medications. Population pharmacokinetic (PopPK) modeling is a valuable tool to guide drug dosing regimens in pregnant women.Areas covered: This narrative review summarizes the current literature on the application of PopPK modeling to optimize drug therapy during human pregnancy. It provides an overview of the physiological changes affecting drug disposition in pregnancy and the basic concepts of PopPK modeling including structural, stochastic, and covariate models. We have conducted an exhaustive literature search (PubMed, Web of Science) spanning May 2014-May 2024 to identify PopPK models in the pregnant population. We have highlighted strategies for model building, evaluation, and interpretation with a focus on identifying clinically relevant covariates that inform dose individualization. Case studies illustrating the utility of PopPK models in guiding dosing recommendations for specific drugs are discussed.Expert opinion: Covariate identification can lead to improved mechanistic understanding of drug disposition and establishment of improved dosing regimens during pregnancy. Insufficient data across trimesters may limit the ability of PopPK models to capture time-varying gestational effects.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"143-160"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0