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This study aimed to establish physiologically based pharmacokinetic\u2013pharmacodynamic (PBPK\u2013PD) models for normal and CIRI rats and to quantitatively characterize the time\u2013concentration\u2013effect relationship, as well as disease-specific mechanistic differences. A middle cerebral artery occlusion rat model was established. STS was administered via the tail vein, and blood samples were collected at serial time points. High-performance liquid chromatography and enzyme-linked immunosorbent assay were used to quantify plasma STS concentrations and inflammatory markers, respectively, whereas equilibrium dialysis was performed to determine protein binding. PK-Sim and Python were used to establish a PBPK model, which was subsequently extrapolated to humans to construct PBPK\u2013PD models. The results showed that plasma STS concentrations were consistently higher in the model rats than in normal rats. STS significantly reduced inflammatory levels in model rats, with a delayed onset of pharmacological effect. Human PBPK model simulations indicated that STS is rapidly eliminated in healthy individuals, while its elimination is reduced under pathological conditions. This study provides a robust modeling framework and methodological reference for dose optimization and prediction of clinical efficacy of STS in the treatment of CIRI.<\/jats:p>","DOI":"10.3390\/biology15110827","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Physiologically Based Pharmacokinetic\u2013Pharmacodynamic-Based Quantification of Exposure\u2013Response for Sodium Tanshinone IIA Sulfonate in Normal and Cerebral Ischemia\u2013Reperfusion Injury Rats"],"prefix":"10.3390","volume":"15","author":[{"given":"Ying","family":"Chen","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of High-Level Biosafety and Biomedical Transformation, School of Public Health, Hangzhou Medical College, Hangzhou 311305, China"},{"name":"Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of High-Level Biosafety and Biomedical Transformation, School of Public Health, Hangzhou Medical College, Hangzhou 311305, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of High-Level Biosafety and Biomedical Transformation, School of Public Health, Hangzhou Medical College, Hangzhou 311305, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Qin","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of High-Level Biosafety and Biomedical Transformation, School of Public Health, Hangzhou Medical College, Hangzhou 311305, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4133-5483","authenticated-orcid":false,"given":"Li","family":"Yu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of High-Level Biosafety and Biomedical Transformation, School of Public Health, Hangzhou Medical College, Hangzhou 311305, China"},{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of High-Level Biosafety and Biomedical Transformation, School of Public Health, Hangzhou Medical College, Hangzhou 311305, China"},{"name":"Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province, Center of Safety Evaluation and Research, Hangzhou Medical College, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, Q., Xu, J., Zhang, J., Tan, J., Wang, Z., Wang, D., and Zhou, Z. 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