Clinical Pharmacology & Therapeutics最新文献

{"title":"CYP2D6-Guided Opioid Therapy for Chronic Pain: A Multi-Center Pragmatic Randomized Controlled Trial.","authors":"Todd C Skaar, Rachel A Myers, Roger B Fillingim, John T Callaghan, Kerri L Cavanaugh, Hrishikesh Chakraborty, Jordan F Baye, Emily J Cicali, Michael T Eadon, Erica N Elwood, Elizabeth C Harris, Lindsay J Hines, Khoa A Nguyen, Michelle A Ramos, Marc Rosenman, Azita Sadeghpour, Saskia Shuman, Rajbir Singh, Emma M Tillman, Christina M Wyatt, Carol R Horowitz, Deepak Voora, Lori A Orlando, Josh F Peterson, Larisa H Cavallari, Julie A Johnson, Paul R Dexter","doi":"10.1002/cpt.70505","DOIUrl":"10.1002/cpt.70505","url":null,"abstract":"<p><p>The analgesic effectiveness of several opioids depends on CYP2D6-mediated metabolism to more active opioid receptor agonists. CYP2D6 activity is impacted by genetic variability and medications that inhibit CYP2D6. We conducted a pragmatic, multi-center, randomized, controlled trial to determine whether CYP2D6-guided opioid prescribing improves chronic pain. Participants were adults recruited from primary care or pain specialty clinics with at least 3 months of chronic pain treated or considered for treatment with tramadol, hydrocodone, or codeine. Participants were randomized to the usual care or CYP2D6-guided arm, in which CYP2D6 pharmacogenetic testing was performed. Healthcare professionals were recommended to avoid tramadol, hydrocodone, or codeine in patients with CYP2D6 intermediate or poor or ultra-rapid (for safety) metabolizer phenotypes based on either genotype or drug interactions. The primary outcome was the change in composite pain intensity scores from baseline to 3 months. Of 1048 enrolled participants, 282 had an actionable CYP2D6 phenotype. In this group, CYP2D6-guided recommendations did not improve the change in composite pain intensity scores from baseline to 3 months compared with usual care (mean [SD] -0.8 [2.4] vs. -0.7 [2.3]) or improve drug-gene concordance (26.8% vs. 27.1%) in the CYP2D6-guided versus usual care arm, respectively. In an exploratory analysis, participants whose therapy changed to align with their CYP2D6 phenotype had significantly improved pain scores. In conclusion, incorporating CYP2D6-guided recommendations for opioid therapy into routine practice did not change prescribing sufficiently to assess its impact on chronic pain control, suggesting that EHR-integrated CYP2D6 guidance is insufficient to change opioid prescribing for chronic pain.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190364","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 Pregnancy and Pediatric Science through the NIH Transporter Elucidation Network.","authors":"Joanne Wang, Jashvant D Unadkat, Samuel Lm Arnold, John K Fallon, Pouria Fattahi, Dan Dongeun Huh, Nicholas Ieronimakis, Edward J Kelly, Svetlana Lutsenko, Robert M Stroud, Jacqueline B Tiley, Jia Yang, Xujia Zhou, Hao Zhu, Rajini Rao, Kathleen M Giacomini, Lauren M Aleksunes","doi":"10.1002/cpt.70517","DOIUrl":"10.1002/cpt.70517","url":null,"abstract":"<p><p>Human gestation is characterized by dynamic changes in maternal physiology and maturation of tissue functions before and after birth. The fetus and neonate are highly dependent upon transfer of maternal nutrients via the placenta and lactating mammary gland, which frequently involve selective membrane transporter proteins. At the same time, developmental changes in fetal and infant transport mechanisms critical for regulating absorption at the intestinal and blood-brain barriers are occurring. Coordinate regulation of cellular entry and efflux of nutrients, supplements, and xenobiotics, including drugs and environmental chemicals, must occur during this critical developmental period. In 2023, the National Institutes of Health launched the Transporter Elucidation Network (TEN) across four centers. This initiative applies experimental, computational, and translational approaches to (1) identify SoLute Carrier (SLC) superfamily and ATP-binding cassette (ABC) transporters in the human placenta, mammary gland, as well as the pediatric brain and intestinal barriers and, (2) characterize their localization, expression, function, and regulation. The Network seeks to identify functional determinants of transporters as gatekeepers of entry to placenta, mammary gland and brain, and applies structural biology, proteomics, metabolomics, organoids, liquid biopsies, and microphysiological systems to this end. Computational strategies, such as machine learning, virtual screening, physiologically based pharmacokinetics, and perinatal epidemiology complement our experimental approaches. This paper highlights the TEN's multidisciplinary strategies to address current challenges in perinatal and pediatric transporter research and its commitment to advancing state-of-the-art tools and new approach methodologies to fill critical gaps in our understanding of nutrient and xenobiotic exposure during early human development.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190380","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":"Toward a Platform PBPK Model to Characterize the Plasma and Tissue Disposition of Unconjugated Antisense Oligonucleotides and GalNAc-Conjugated Small Interfering RNAs in Preclinical Species and Human.","authors":"Devam A Desai, Rodrigo Cristofoletti","doi":"10.1002/cpt.70524","DOIUrl":"10.1002/cpt.70524","url":null,"abstract":"<p><p>Unconjugated antisense oligonucleotides (ASOs) and GalNAc-conjugated small interfering RNAs (siRNAs) have emerged as transformative therapeutic modalities, but their translation remains hindered by complex pharmacokinetics characterized by rapid plasma clearance, heterogeneous tissue uptake, and prolonged intracellular retention. Physiologically based pharmacokinetic (PBPK) modeling offers a mechanistic framework to integrate these processes across species, yet applications to oligonucleotides remain limited, and existing efforts are typically restricted to specific chemistries or routes of administration. This study aimed to develop a cross-species PBPK platform to characterize the plasma and tissue disposition of unconjugated ASOs and GalNAc-siRNAs in preclinical species and humans, and to evaluate the consistency of estimated drug-specific parameters with pre-specified allometric scaling relationships within the domain of compounds and routes considered. Published datasets spanning mice, rats, non-human primates, and humans were integrated for representative unconjugated ASOs (Malat-1, GluR1, p-tau, tominersen) and GalNAc-siRNAs (ALN-AT3, givosiran, fitusiran). The PBPK model incorporated 11 tissue compartments, cerebrospinal fluid substructures, tissue substructures, endosomal trafficking, non-specific binding in kidney and liver, and ASGPR-mediated internalization for GalNAc-siRNAs. Parameters for endocytosis, exocytosis, and degradation were estimated, and estimated values were compared with pre-specified allometric exponents to assess physiological plausibility (i.e., as a consistency check rather than independent inference of scaling laws). The model captured plasma, liver, kidney, and CNS profiles across species, reproducing rapid systemic clearance with prolonged tissue half-lives. Estimated parameter values for endocytosis, exocytosis, and non-specific kidney binding were consistent with pre-specified allometric exponents (b = -0.25 and -0.2, respectively), supporting the physiological plausibility of the estimates. Sensitivity analyses identified endocytosis and rate of degradation as dominant determinants of systemic and tissue disposition. This work establishes a translational PBPK platform for unconjugated ASOs and GalNAc-conjugated siRNAs, enabling quantitative interspecies extrapolation within the domain of the compounds, routes, and species studied. The framework provides a mechanistic basis to support dose selection, safety assessment, and clinical translation for these subclasses; extrapolation to other oligonucleotide subclasses (e.g., GalNAc-ASOs, unconjugated siRNAs, LNP-formulated oligonucleotides) will require additional datasets and dedicated validation.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190317","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":"Reprocessing Mass Spectra from Therapeutic Drug Monitoring to Unveil Proton Pump Inhibitor Use and Quantify Phenoconversion of Escitalopram Metabolism in CYP2C19-Genotyped Patients.","authors":"Kristine Hole, Birgit M Wollmann, Julia Carolin Stingl, Espen Molden","doi":"10.1002/cpt.70506","DOIUrl":"10.1002/cpt.70506","url":null,"abstract":"<p><p>Escitalopram is a frequently prescribed antidepressant drug. CYP2C19 genotype is a major determinant of escitalopram metabolism and treatment outcome. However, real-life studies show a high degree of genotype-phenotype mismatch in escitalopram metabolism. The present study aimed to identify comedication with proton pump inhibitors (PPIs) and quantify phenoconversion of escitalopram metabolism in CYP2C19-genotyped patients by reprocessing high-resolution mass spectra from therapeutic drug monitoring (TDM) analyses. Patients were included from a combined TDM/pharmacogenetics (PGx) laboratory facility in Oslo, Norway. TDM profiles of escitalopram and CYP2C19 genotypes were available in the laboratory database. Reprocessing of high-resolution mass spectra by exact mass and fragment detection identified possible comedication with pantoprazole, esomeprazole/omeprazole or lansoprazole using mzCloud reference library. Patients were grouped as normal metabolizers (NMs), intermediate metabolizers (IMs), poor metabolizers (PMs), rapid metabolizers (RM), or ultrarapid metabolizers (UM). Primary outcome measure was N-desmethylescitalopram-to-escitalopram metabolic ratio (MR; CYP2C19 biomarker) in UMs vs. PMs. 2818 patients were included, constituting 2373 without and 445 (15.8%) with PPIs. Most patients were females (64.2%). Regarding CYP2C19 phenotype distribution, the cohort comprised 39.3% NMs, 29.3% IMs, 2.6% PMs, 24.6% RMs, and 4.2% UMs. Escitalopram MR was 4.5-fold higher in CYP2C19 UMs vs. PMs without PPIs (P < 0.001), while this difference was 2.8-fold in pantoprazole users (P < 0.001), and 1.8-fold in esomeprazole/omeprazole users (P = 0.2). In conclusion, PPIs show significant phenoconversion of CYP2C19-mediated escitalopram metabolism with esomeprazole/omeprazole exhibiting a stronger effect than pantoprazole. The novel method for identification of interacting comedications in TDM samples illustrates the innovative potential of high-resolution mass spectrometry in precision medicine.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178279","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":"Overview of Regulatory Guidelines Related to Methods and Models for Small Populations.","authors":"Laurens Sluijterman, Letao Li, Kristin E Karlsson, Vincent Damotte, Sarah Zohar, Kit Roes, Joanna IntHout","doi":"10.1002/cpt.70523","DOIUrl":"https://doi.org/10.1002/cpt.70523","url":null,"abstract":"<p><p>This paper provides an overview of approaches and related guidelines from the EMA, FDA, and ICH that are relevant for obtaining clinical evidence for small populations to support regulatory decision making. The approaches are grouped into three categories: (1) maximizing the attainable sample size, (2) adapting the trial design to deal with a small sample size, and (3) including external information, while also examining the role of modeling. Guidelines for clinical trials, guidelines specifically for small populations, as well as guidelines that include the use of modeling to support clinical evidence were included in the review. A recurring theme throughout the guidelines is the critical importance of the clinical context, affecting both the evidentiary standard and which approaches and models are acceptable. Two key gaps were identified: (1) guidance on Bayesian approaches is limited, and (2) there is no clear guidance on how to synthesize evidence across different modalities, such as trial results and Real-World Data, from both a practical and regulatory perspective.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178295","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":"Unbound Intrinsic Formation Clearance of 6β-Hydroxycortisol Is a Useful Biomarker of CYP3A4 Activity during Pregnancy.","authors":"Aurora K Authement, Mary F Hebert, Emily E Fay, Nina Isoherranen","doi":"10.1002/cpt.70519","DOIUrl":"10.1002/cpt.70519","url":null,"abstract":"<p><p>Pregnancy results in multiple physiological changes that impact drug disposition. For example, hepatic CYP3A activity and renal transporter-mediated clearance increase in late pregnancy, but the time course of these changes across pregnancy is not known. Endogenous biomarkers offer a minimally invasive approach to characterize pharmacokinetic changes during pregnancy and postpartum. The goal of this study was to determine whether 6β-OH-cortisol formation clearance (CL_f,OHCOL) can be used as a biomarker of hepatic CYP3A activity during pregnancy. Thus, we measured cortisol, cortisone, and 6β-OH-cortisol in plasma and urine from 47 women during late pregnancy and postpartum and calculated the CL_f,OHCOL, unbound fraction (f_u), unbound intrinsic CL_f (CL_{f,u,int,OHCOL}), and renal clearance (CL_r). CL_f,OHCOL increased 1.3-fold in late pregnancy while cortisol f_u decreased significantly. CL_{f,u,int,OHCOL} increased 1.8-fold, corresponding to a 2.1-fold increase in hepatic CYP3A activity. The increase in CL_{f,u,int,OHCOL} was observed in CYP3A5 expressors and in CYP3A5 nonexpressors. In late pregnancy, the increase in CL_r,cortisol and CL_r,OHCOL exceeded the calculated increase in filtration clearance, suggesting increased transporter-mediated secretion. The decreased f_u of cortisol during pregnancy was captured by a model incorporating increased expression of corticosteroid binding globulin (CBG) and increased binding affinity of cortisol to CBG. These data suggest that CL_{f,u,int,OHCOL} is a robust biomarker of CYP3A activity during pregnancy and could be used in future studies to characterize the time course of changes in CYP3A activity across gestation and postpartum. Further, CL_r,cortisol and CL_r,OHCOL may be biomarkers of kidney OCT and MATE activity and could be used to evaluate kidney transporter activity during pregnancy.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163429","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":"Obstetric Pharmacomicrobiomics.","authors":"Ahizechukwu C Eke","doi":"10.1002/cpt.70520","DOIUrl":"10.1002/cpt.70520","url":null,"abstract":"<p><p>Pregnancy is characterized by physiologic, metabolic, immunologic, and microbial adaptation. Medication use during pregnancy is common. Yet, therapeutic response often remains unpredictable because obstetric pharmacology has historically focused on pharmacokinetic changes while paying little attention to host-microbiome-drug interactions. Pharmacomicrobiomics, the study of bidirectional interactions between the microbiome and therapeutic agents, has emerged as an important frontier in precision medicine. Increasing evidence demonstrates that the maternal microbiome may influence drug bioavailability, metabolism, efficacy, toxicity, immune response, and placental signaling during pregnancy. Conversely, medications used in obstetric practice, including antibiotics, antiretrovirals, metformin, iron supplementation, and proton pump inhibitors, may reshape maternal microbial ecosystems with downstream implications for maternal-fetal health. Pregnancy introduces pharmacomicrobiomic complexity because the maternal gut, vaginal, and oral microbial communities evolve across gestation, while the placenta and fetus are exposed to microbial metabolites and microbe-associated signals without convincing evidence of stable resident microbiomes. Emerging data suggest that microbial composition may influence preterm birth, hypertensive disorders of pregnancy, gestational diabetes mellitus, obesity, fetal growth, immune development, and therapeutic responsiveness. This mini-review examines recent advances in obstetric pharmacomicrobiomics with emphasis on microbial regulation of drug metabolism, pregnancy-associated microbial remodeling, microbiome-mediated therapeutic variability, placental and fetal implications, and future translational applications. We propose that obstetric pharmacology is entering a systems biology era in which the maternal microbiome should be investigated as a potentially important determinant of therapeutic response rather than treated solely as a background physiologic variable. Integrating microbiome science into maternal-fetal therapeutics may ultimately improve individualized treatment strategies, drug development, and precision obstetric pharmacology.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134576","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":"The Future of all-Comers Trials in the Era of Precision Oncology.","authors":"J Andrew Williams, Nitin Jain, Caroline MacNish Porter, Bowen Cui, Thorsten S Gutjahr","doi":"10.1002/cpt.70521","DOIUrl":"10.1002/cpt.70521","url":null,"abstract":"<p><p>Approvals of new therapeutics are increasingly restricted to specified biomarker subgroups, even where pivotal clinical studies meet primary endpoints in broader \"all-comers\" populations. In this article, we discuss the potential factors that increase the likelihood of approvals in biomarker subpopulations rather than all-comers. We outline mitigation strategies drug developers can pursue to plan for potential label restrictions and achieve companion diagnostic readiness, ensuring patients receive timely access to innovative medicines.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134611","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":"From Phase Ib/II to Seamless Phase II/III: A Simulation-Based Discussion of Design Strategies for Dose Optimization and Confirmatory Phase.","authors":"Annan Deng, Xiaochen Zhu, Haiyang Sheng, Yiwei Li, Tian Chen, Shu-Pang Huang","doi":"10.1002/cpt.70522","DOIUrl":"10.1002/cpt.70522","url":null,"abstract":"<p><p>The emergence of targeted therapies and immunotherapies has challenged the traditional \"more is better\" paradigm underlying maximum tolerated dose (MTD)-based trials, as dose escalation beyond receptor saturation often yields limited additional efficacy while substantially increasing toxicity. In response, the U.S. Food and Drug Administration's Project Optimus emphasizes dose optimization (DO) prior to confirmatory studies to ensure a favorable benefit-risk profile. Motivated by this shift, we systematically evaluate strategies for incorporating DO at different stages of oncology drug development. We compare three approaches: (1) DO combined with proof-of-concept in a seamless Phase Ib/II study prior to a registrational trial; (2) DO conducted in an operational seamless Phase II/III design; and (3) DO embedded within an inferential seamless Phase II/III design. Simulation studies were performed across a range of efficacy-toxicity scenarios to assess dose-selection accuracy, statistical operating characteristics, expected sample size, and overall study duration. Under the simulated settings, both the Phase Ib/II DO strategy and the inferential seamless Phase II/III design reduced total development time compared with the operational seamless approach. The inferential seamless design achieved the lowest expected sample size and the shortest average trial duration while maintaining high power under the primary simulated scenarios. The comparative performance of the three strategies also depended on how well the short-term dose-selection endpoints predicted long-term survival. Overall, DO can be effectively implemented at multiple stages of clinical development. The optimal strategy should balance statistical rigor, development speed, practical feasibility, and the suitability of the endpoints used for dose selection.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134606","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":"Medication Use During Breastfeeding-An Understudied Population: A Five-Year Experience in the Pharmacovigilance Center of Lyon.","authors":"Blandine Bertin, Aurore Gouraud, Anthony Facile, Fanny Ledys, Sabrina Pierre, Véronique Pizzoglio, Thierry Vial, Marine Auffret, Marina Atzenhoffer","doi":"10.1002/cpt.70518","DOIUrl":"10.1002/cpt.70518","url":null,"abstract":"<p><p>Medication use during breastfeeding is common, yet data on drug transfer into breast milk and infant exposure remain limited. This study describes real-world requests concerning medication compatibility with breastfeeding managed by the Lyon pharmacovigilance center over five years. We conducted a descriptive observational study including all requests recorded between January 2019 and December 2023. Characteristics of infants, medications involved, and recommendations provided were analyzed. A total of 2,473 requests were included, corresponding to approximately 500 per year. Most requests originated from patients (44%), allied health professionals (29%), or specialists (25%), with two thirds occurring postpartum. Overall, our recommendations supported breastfeeding in 87% of cases, either unconditionally or under specific conditions, such as clinical monitoring, therapeutic adjustments, or timing strategies. Only 13% of cases resulted in an unfavorable recommendation, for either treatment or breastfeeding discontinuation, due to formal contraindications, insufficient therapeutic benefit, or limited safety data. Polytherapy was observed in 35% of cases and was associated with more restrictive recommendations. Medications used for chronic conditions accounted for 36% of cases such as antihypertensives, antiepileptics, or psychotropic agents. Treatments for acute conditions included anti-infectives, analgesics, contrast agents, or anesthetics. Reported adverse effects in infants were rare and non-serious. In most cases, a recommendation supporting breastfeeding during maternal treatment, with or without conditions, was provided. However, uncertainty persists, particularly in complex or poorly documented situations. This work highlights the need for reliable, accessible information, inclusion of breastfeeding women in clinical research, and strengthened regulatory and postmarketing evaluation strategies to ensure infant safety health.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101415","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}