{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:46:59Z","timestamp":1777866419696,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Nimodipine is routinely used in aneurysmal subarachnoid hemorrhage (aSAH), but the optimal route of administration remains uncertain. Intravenous and enteral delivery differ in pharmacokinetics, yet the clinical relevance of these differences is unclear. This scoping review aimed to map evidence on the pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous and enteral nimodipine and their relationship with clinical outcomes. Methods: A scoping review was conducted following PRISMA-ScR guidelines. PubMed, Scopus, and Web of Science were searched from 1982 to March 2026. Studies in adult aSAH patients reporting PK and\/or PD outcomes after intravenous or enteral nimodipine were included. Data were synthesized qualitatively. Results: Twenty studies were included. Intravenous administration provided higher and more consistent systemic exposure, whereas enteral administration showed low and highly variable bioavailability, particularly via nasogastric tubes. Despite these differences, pharmacodynamic effects were not clearly related to systemic concentrations, and hypotension occurred similarly across routes. Evidence on cerebral physiology was limited. Randomized studies showed no significant differences in delayed cerebral ischemia, infarction, or functional outcomes between routes. Conclusions: Pharmacokinetic advantages of intravenous nimodipine do not consistently translate into pharmacodynamic or clinical benefits, although available evidence is limited and heterogeneous. The PK\u2013PD relationship appears weak, and further research is needed to guide optimized administration strategies.<\/jats:p>","DOI":"10.3390\/jcm15093425","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:03:47Z","timestamp":1777536227000},"page":"3425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic and Pharmacodynamic Profiles of Intravenous and Enteral Nimodipine in Patients with Aneurysmal Subarachnoid Hemorrhage: A Scoping Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7555-4872","authenticated-orcid":false,"given":"Marco","family":"Sanvitti","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, \u201cSapienza\u201d University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada","family":"Iafrate","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University of Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-6646","authenticated-orcid":false,"given":"Federico","family":"Bilotta","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University of Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1161\/STR.0b013e3182587839","article-title":"Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association\/American Stroke Association","volume":"43","author":"Connolly","year":"2012","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0140-6736(16)30668-7","article-title":"Spontaneous Subarachnoid Haemorrhage","volume":"389","author":"Macdonald","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1161\/STROKEAHA.110.589275","article-title":"Definition of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage as an Outcome Event in Clinical Trials and Observational Studies: Proposal of a Multidisciplinary Research Group","volume":"41","author":"Vergouwen","year":"2010","journal-title":"Stroke"},{"key":"ref_4","first-page":"CD000277","article-title":"Calcium Antagonists for Aneurysmal Subarachnoid Haemorrhage","volume":"2007","author":"Rinkel","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","first-page":"e314","article-title":"2023 Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association\/American Stroke Association","volume":"54","author":"Hoh","year":"2023","journal-title":"Stroke"},{"key":"ref_6","first-page":"302","article-title":"Considerations When Administering Medications Enterally in the Critically Ill","volume":"26","author":"MacLaren","year":"2023","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00701-015-2369-9","article-title":"Serum Levels of Nimodipine in Enteral and Parenteral Administration in Patients with Aneurysmal Subarachnoid Hemorrhage","volume":"157","author":"Abboud","year":"2015","journal-title":"Acta Neurochir."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100","DOI":"10.18433\/jpps30960","article-title":"The Impact of Nimodipine Administration through Feeding Tube on Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage","volume":"23","author":"Isse","year":"2020","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40262-023-01213-x","article-title":"Pharmacokinetic Alterations Associated with Critical Illness","volume":"62","author":"Dresser","year":"2023","journal-title":"Clin. Pharmacokinet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/phar.2791","article-title":"Comparison of Nimodipine Formulations and Administration Techniques via Enteral Feeding Tubes in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Cohort Study","volume":"43","author":"Mahmoud","year":"2023","journal-title":"Pharmacotherapy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/STROKEAHA.116.014250","article-title":"Randomized, Open-Label, Phase 1\/2a Study to Determine the Maximum Tolerated Dose of Intraventricular Sustained Release Nimodipine for Subarachnoid Hemorrhage (NEWTON [Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage])","volume":"48","author":"Etminan","year":"2017","journal-title":"Stroke"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s12028-023-01760-y","article-title":"Blood Pressure Changes in Association with Nimodipine Therapy in Patients with Spontaneous Subarachnoid Hemorrhage","volume":"39","author":"Rass","year":"2023","journal-title":"Neurocrit. Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e34789","DOI":"10.1097\/MD.0000000000034789","article-title":"The Efficacy of Different Nimodipine Administration Route for Treating Subarachnoid Hemorrhage: A Network Meta-Analysis","volume":"102","author":"Lei","year":"2023","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan-a Web and Mobile App for Systematic Reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111940","DOI":"10.1016\/j.jocn.2026.111940","article-title":"Nimodipine Dosing and Pharmacokinetic Variability in Subarachnoid Hemorrhage Patients","volume":"147","author":"Bellapart","year":"2026","journal-title":"J. Clin. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kumar, A., D\u2019Andrea, C., Kohli, P., Kottayil, S.G., Longstreth, J., and Macdonald, R.L. (2025). Phase 1, Randomized, Crossover Study Comparing Intravenous GTX-104 to Oral Nimodipine in Healthy Human Subjects. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0323162"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"125666","DOI":"10.1016\/j.jns.2025.125666","article-title":"Impact of Cerebral Vasospasm Therapy on Nimodipine Exposure in Subarachnoid Hemorrhage: A Population Pharmacokinetic Study","volume":"479","author":"Foucher","year":"2025","journal-title":"J. Neurol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mahmoud, S.H., Hefny, F., Isse, F.A., Farooq, S., Ling, S., O\u2019Kelly, C., and Kutsogiannis, D.J. (2024). Nimodipine Systemic Exposure and Outcomes Following Aneurysmal Subarachnoid Hemorrhage: A Pilot Prospective Observational Study (ASH-1 Study). Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1233267"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/ANA.0000000000000928","article-title":"The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage","volume":"36","author":"Moser","year":"2024","journal-title":"J. Neurosurg. Anesthesiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"G\u00f6ttsche, J., Schweingruber, N., Groth, J.C., Gerloff, C., Westphal, M., and Czorlich, P. (2021). Safety and Clinical Effects of Switching From Intravenous to Oral Nimodipine Administration in Aneurysmal Subarachnoid Hemorrhage. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.748413"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/BF00265956","article-title":"Investigation of Nimodipine Pharmacokinetics in Chinese Patients with Acute Subarachnoid Haemorrhage","volume":"45","author":"Kumana","year":"1993","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12028-019-00676-w","article-title":"Incidence of Arterial Hypotension in Patients Receiving Peroral or Continuous Intra-Arterial Nimodipine After Aneurysmal or Perimesencephalic Subarachnoid Hemorrhage","volume":"31","author":"Kieninger","year":"2019","journal-title":"Neurocrit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1177\/1060028018778751","article-title":"Impact of Early Versus Late Intravenous Followed by Oral Nimodipine Treatment on the Occurrence of Delayed Cerebral Ischemia Among Patients with Aneurysm Subarachnoid Hemorrhage","volume":"52","author":"Samseethong","year":"2018","journal-title":"Ann. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.wneu.2017.02.014","article-title":"Effect of Intra-Arterial and Intravenous Nimodipine Therapy of Cerebral Vasospasm After Subarachnoid Hemorrhage on Cerebrovascular Reactivity and Oxygenation","volume":"101","author":"Hockel","year":"2017","journal-title":"World Neurosurg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.wneu.2017.03.062","article-title":"Systemic and Cerebral Concentration of Nimodipine During Established and Experimental Vasospasm Treatment","volume":"102","author":"Albanna","year":"2017","journal-title":"World Neurosurg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.wneu.2011.09.030","article-title":"A Randomized Outcome Study of Enteral versus Intravenous Nimodipine in 171 Patients After Acute Aneurysmal Subarachnoid Hemorrhage","volume":"78","author":"Soppi","year":"2012","journal-title":"World Neurosurg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3171\/2008.7.JNS08178","article-title":"Nimodipine in Aneurysmal Subarachnoid Hemorrhage: A Randomized Study of Intravenous or Peroral Administration","volume":"110","author":"Kronvall","year":"2009","journal-title":"J. Neurosurg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00228-007-0267-7","article-title":"Early-Phase Pharmacokinetics of Enteral and Parenteral Nimodipine in Patients with Acute Subarachnoid Haemorrhage\u2014A Pilot Study","volume":"63","author":"Soppi","year":"2007","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/BF00607954","article-title":"Pharmacokinetics of Nimodipine in Patients with Aneurysmal Subarachnoid Haemorrhage","volume":"30","author":"Vinge","year":"1986","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1055\/s-2008-1054107","article-title":"Overview on Pharmacokinetics of Nimodipine in Healthy Volunteers and in Patients with Subarachnoid Hemorrhage","volume":"28","author":"Ahr","year":"1985","journal-title":"Minim. Invasive Neurosurg."},{"key":"ref_32","first-page":"165","article-title":"Pharmacokinetics of Intravenous and Oral Nimodipine in ICU Patients with a Subarachnoid Haemorrhage","volume":"146","author":"Sanders","year":"2011","journal-title":"Pharm. Weekbl."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zou, T., He, H., Wu, Y., Xie, X., and Yin, W. (2025). Gastrointestinal Dysfunction in Aneurysmal Subarachnoid Hemorrhage: Prevalence, Clinical Correlates, and Prognostic Implications from a 15-Year ICU Cohort Study. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1694188"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ijpharm.2014.11.065","article-title":"Quantitative Analysis of Drug Losses Administered via Nasogastric Tube--In Vitro Study","volume":"478","author":"Suk","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/jcpt.12041edit","article-title":"Therapeutic Concerns When Oral Medications Are Administered Nasogastrically","volume":"38","author":"Zhu","year":"2013","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/JNN.0000000000000625","article-title":"Nimodipine in Clinical Practice: A Pharmacological Update","volume":"54","author":"Clough","year":"2022","journal-title":"J. Neurosci. Nurs."},{"key":"ref_37","first-page":"293","article-title":"The Influence of Age on the Pharmacokinetics of Nimodipine","volume":"34","author":"Breuel","year":"1996","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/j.1365-2125.1991.tb03908.x","article-title":"Differential Effects of Valproic Acid and Enzyme-Inducing Anticonvulsants on Nimodipine Pharmacokinetics in Epileptic Patients","volume":"32","author":"Tartara","year":"1991","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/j.1749-6632.1988.tb33415.x","article-title":"Pharmacology of Nimodipine. A Review","volume":"522","author":"Scriabine","year":"1988","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"176718","DOI":"10.1016\/j.ejphar.2024.176718","article-title":"Nimodipine Inhibits Spreading Depolarization, Ischemic Injury, and Neuroinflammation in Mouse Live Brain Slice Preparations","volume":"977","author":"Frank","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1111\/bph.70060","article-title":"Nimodipine Reduces Microglial Activation in Vitro as Evidenced by Morphological Phenotype, Phagocytic Activity and High-Throughput RNA Sequencing","volume":"182","author":"Pesti","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/cpt.3499","article-title":"Cerebral Ischemia Protection After Aneurysmal Subarachnoid Hemorrhage: CSF Nimodipine Levels After Intravenous Versus Oral Nimodipine Administration","volume":"117","author":"Moser","year":"2025","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/WNF.0000000000000356","article-title":"Cerebrospinal Fluid Concentrations of Nimodipine Correlate with Long-Term Outcome in Aneurysmal Subarachnoid Hemorrhage: Pilot Study","volume":"42","author":"Riva","year":"2019","journal-title":"Clin. Neuropharmacol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/9\/3425\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:39:46Z","timestamp":1777538386000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/9\/3425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcm15093425"],"URL":"https:\/\/doi.org\/10.3390\/jcm15093425","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]}}}