{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:58:35Z","timestamp":1772211515424,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ratiopharm GmbH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Ephedrine and cafedrine\/theodrenaline (C\/T) are established treatments for spinal anesthesia-induced hypotension during cesarean section. Both aim to stabilize maternal blood pressure and enhance neonatal oxygenation. We compared their effects on maternal hemodynamics and neonatal acid-base status using population kinetic\/pharmacodynamic (K\/PD) modeling and multiple regression analysis. Methods: The multicenter, prospective, open-label, two-armed, non-interventional HYPOTENS study included 243 parturients undergoing spinal anesthesia for elective cesarean section in Germany. Hypotension was treated with intravenous boluses of either C\/T (10\u2013200 mg, 55.6%) or ephedrine (5\u201340 mg, 44.4%), with dosing determined by the attending anesthesiologist. Maternal mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were recorded for 30 min after treatment. Neonatal acidosis biomarkers included umbilical arterial pH, base excess (BE), and lactate. Results: A population K\/PD model captured an initial increase followed by a plateau in MAP, SBP and HR after treatment. Maximum HR (MAXHR) was 15% higher after ephedrine than after C\/T (p &lt; 0.001). BMI and spinal block height significantly influenced maternal hemodynamics (both p &lt; 0.001). Neonatal biomarkers were associated with the duration of maternal MAP below pre-surgery levels, gestational age, spinal block height, antihypotensive treatment, bupivacaine dose, and MAXHR (all p &lt; 0.05). Conclusions: Ephedrine was associated with higher maternal MAXHR. Notably, higher maternal MAXHR was correlated with lower neonatal BE, suggesting that lower maternal peak HR may benefit. These findings may support the use of substances that are largely inert with respect to maternal HR.<\/jats:p>","DOI":"10.3390\/pharmaceutics18030296","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:52:38Z","timestamp":1772207558000},"page":"296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacometric Analysis of Cafedrine\/Theodrenaline Versus Ephedrine on Maternal Hemodynamics and Neonatal Acidosis During Cesarean Section"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6550-2819","authenticated-orcid":false,"given":"Christiane","family":"Dings","sequence":"first","affiliation":[{"name":"Saarmetrics GmbH, 66123 Saarbr\u00fccken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8372-1465","authenticated-orcid":false,"given":"Thorsten","family":"Lehr","sequence":"additional","affiliation":[{"name":"Saarmetrics GmbH, 66123 Saarbr\u00fccken, Germany"},{"name":"Clinical Pharmacy, Department of Pharmaceutical Science, Saarland University, 66123 Saarbr\u00fccken, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5324-981X","authenticated-orcid":false,"given":"Peter","family":"Kranke","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Vojnar","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Giessen and Marburg, Campus Marburg, Philipps University of Marburg, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1872-6558","authenticated-orcid":false,"given":"Christine","family":"Gaik","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital Giessen and Marburg, Campus Marburg, Philipps University of Marburg, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tilo","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Philipps University Marburg, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leopold","family":"Eberhart","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, Philipps University Marburg, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0653-234X","authenticated-orcid":false,"given":"Susanne","family":"Huljic-Lankinen","sequence":"additional","affiliation":[{"name":"Ratiopharm GmbH, 89079 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1069-218X","authenticated-orcid":false,"given":"Melanie","family":"Murst","sequence":"additional","affiliation":[{"name":"Ratiopharm GmbH, 89079 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Kreuer","sequence":"additional","affiliation":[{"name":"Saarmetrics GmbH, 66123 Saarbr\u00fccken, Germany"},{"name":"Department of Anesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/LRA.S111459","article-title":"Preventing Nausea and Vomiting in Women Undergoing Regional Anesthesia for Cesarean Section: Challenges and Solutions","volume":"10","author":"Jelting","year":"2017","journal-title":"Local Reg. 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