{"id":227512,"date":"2025-12-20T01:28:00","date_gmt":"2025-12-20T07:28:00","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2025\/12\/model-informed-dose-optimization-of-spironolactone-in-neonates-and-infants"},"modified":"2025-12-20T01:28:00","modified_gmt":"2025-12-20T07:28:00","slug":"model-informed-dose-optimization-of-spironolactone-in-neonates-and-infants","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2025\/12\/model-informed-dose-optimization-of-spironolactone-in-neonates-and-infants","title":{"rendered":"Model-Informed Dose Optimization of Spironolactone in Neonates and Infants"},"content":{"rendered":"<p style=\"padding-right: 20px\"><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/model-informed-dose-optimization-of-spironolactone-in-neonates-and-infants2.jpg\"><\/a><\/p>\n<p>Background\/Objectives: Spironolactone (SP) has been used off-label in pediatrics since its approval, but its use is challenged by limited pharmacokinetic (PK) data in adults and especially in children. Methods: Physiologically based pharmacokinetic (PBPK) models for SP and its active metabolites, canrenone (CAN) and 7\u03b1 thio-methyl spironolactone (TMS), in adults were developed. These models aim to enhance understanding of SP\u2019s PK and provide a basis for predicting PK and optimizing SP dosing in infants and neonates. Given SP\u2019s complex metabolism, we assumed complete conversion to CAN and TMS by CES1 enzymes, fitting CES1-mediated metabolism to the parent-metabolite model using PK data. We incorporated ontogeny for CES1 and CYP3A4 and other age-related physiological changes into the model to anticipate PK in the pediatric population.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Background\/Objectives: Spironolactone (SP) has been used off-label in pediatrics since its approval, but its use is challenged by limited pharmacokinetic (PK) data in adults and especially in children. Methods: Physiologically based pharmacokinetic (PBPK) models for SP and its active metabolites, canrenone (CAN) and 7\u03b1 thio-methyl spironolactone (TMS), in adults were developed. These models aim to [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[269],"tags":[],"class_list":["post-227512","post","type-post","status-publish","format-standard","hentry","category-life-extension"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/227512","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=227512"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/227512\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=227512"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=227512"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=227512"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}