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Over the past decade, disease-modifying therapies targeting the survival motor neuron pathway\u2014nusinersen, onasemnogene abeparvovec, and risdiplam\u2014have significantly transformed the clinical landscape of spinal muscular atrophy. Despite their common therapeutic goal of restoring functional survival motor neuron protein levels, these agents differ markedly in their molecular design, route of administration, pharmacokinetic behavior, and population-specific efficacy. This narrative review provides a comprehensive synthesis of pre- and post-approval pharmacokinetic data from pivotal trials, real-world studies, and population-based modeling. Nusinersen, an intrathecal antisense oligonucleotide, demonstrates prolonged cerebrospinal fluid exposure and slow systemic clearance. Onasemnogene abeparvovec, a single-dose gene therapy, shows sustained survival motor neuron expression mediated by adeno-associated virus 9 vector delivery and episomal persistence in nondividing neurons. Risdiplam, an orally administered survival motor neuron 2 splicing modifier, exhibits systemic bioavailability with reliable central nervous system penetration and predictable pharmacokinetics across age groups. Elimination of gene products and oligonucleotides is a multifaceted process involving enzymatic degradation, immune responses, and excretion through the kidneys or liver. We further discussed how interindividual variability, age, survival motor neuron 2 copy number, and immunological factors influence pharmacokinetic\u2013pharmacodynamic relationships. Personalized treatment strategies for spinal muscular atrophy are increasingly being guided by advances in pharmacokinetic modeling. As the field evolves, biomarker-based monitoring and combination therapies are emerging as promising complementary approaches. With growing clinical experience and an expanding body of pharmacokinetic research on targeted therapies, there is strong potential to further refine treatment strategies\u2014ultimately making spinal muscular atrophy care more effective, safer, and more accessible for patients worldwide.<\/jats:p>","DOI":"10.1177\/03000605251397777","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:28:11Z","timestamp":1764221291000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics of therapies approved for spinal muscular atrophy: A narrative review of current evidence"],"prefix":"10.1177","volume":"53","author":[{"given":"Eda K\u00fcbra","family":"Sel","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Dokuz Eylul University, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira Meni Maria","family":"Gkrinia","sequence":"additional","affiliation":[{"name":"School of Public Health, Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Roncato","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano, Istituti di Ricovero e Cura a Carattere Scientifico, Italy"},{"name":"Department of Medicine, University of Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinko","family":"Vitezi\u0107","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1519-8828","authenticated-orcid":false,"given":"Slobodan","family":"Jankovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, University of Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7848-6600","authenticated-orcid":false,"given":"Andrej","family":"Belan\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On Behalf Of The EACPT Early Career Clinical Pharmacologists Working Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1040858"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(96)90032-2"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-1578(10)60680-0"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-265"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2015.07.004"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S239603"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.06.042"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807305788"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.030148"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64142-7.00057-6"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40271-020-00415-w"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2015.03.010"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00038-7"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.171105098"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg256"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201102"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20548"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.051177"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250127"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20836"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000290830.40544.b9"},{"key":"e_1_3_8_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21241"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07677"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41073-019-0064-8"},{"key":"e_1_3_8_26_2","unstructured":"Center for drug evaluation and research. 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