Academic Journal
Model-informed dose optimization of carvedilol and nebivolol in cirrhotic patients: a pilot randomized clinical study.
| Τίτλος: | Model-informed dose optimization of carvedilol and nebivolol in cirrhotic patients: a pilot randomized clinical study. |
|---|---|
| Συγγραφείς: | Tarek, Mai, Ali, Ahmed A, Biomy, Reda, Abdelkawy, Khaled, El-Khateeb, Eman |
| Πηγή: | Scientific Reports; 6/16/2026, Vol. 16 Issue 1, p1-17, 17p |
| Θεματικοί όροι: | Cirrhosis of the liver, Carvedilol, Portal hypertension, Medical research, Beta adrenoceptors, Pharmacokinetics |
| Περίληψη: | Liver cirrhosis causes physiological and pharmacokinetic alterations that complicate antihypertensive therapy, in the presence of portal and arterial hypertension. This study evaluated the efficacy and safety of PBPK-guided dosing of carvedilol and nebivolol in cirrhotic patients. First, PBPK models were validated using clinical pharmacokinetic data from healthy volunteers and optimized for cirrhosis, then applied to simulate untested cirrhotic populations and estimate unbound plasma exposure across disease stages. Second, a prospective, open-label, parallel randomized pilot study enrolled 44 cirrhotic patients (Child-Pugh; CP-A or B) with arterial hypertension, who received PBPK-guided doses of carvedilol or nebivolol, with 3 months of follow-up including monthly monitoring of adverse events, blood pressure, heart rate, portal hemodynamics by Doppler ultrasound, and laboratory safety parameters. The model predicted dose reductions of carvedilol 25 mg once daily and nebivolol 10 mg once daily to 11.26 mg and 4.98 mg in mild cirrhosis, 5.52 mg and 2.98 mg in moderate cirrhosis, and 1.99 mg and 1.23 mg in severe cirrhosis. Following administration of doses as close as possible to the PBPK-guided doses in CP A and B, both agents were well tolerated, effectively reducing blood pressure and heart rate without significant changes in hepatic and renal parameters. Portal hemodynamics and platelet count improved in both groups, with carvedilol showing greater effects; adverse events were mild and more frequent with carvedilol. While both drugs controlled blood pressure, carvedilol improved portal hemodynamics more. PBPK-guided dosing addressed pharmacokinetic changes, but pharmacodynamic differences between CP-A and CP-B persisted due to disease progression. [ABSTRACT FROM AUTHOR] |
| Copyright of Scientific Reports is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Βάση Δεδομένων: | Complementary Index |
| FullText | Text: Availability: 0 CustomLinks: – Url: https://dx.doi.org/doi:10.1038/s41598-026-56578-3 Name: EDS - Springer Nature Journals (s7799221) Category: fullText Text: View record at Springer – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:edb&genre=article&issn=20452322&ISBN=&volume=16&issue=1&date=20260616&spage=1&pages=1-17&title=Scientific Reports&atitle=Model-informed%20dose%20optimization%20of%20carvedilol%20and%20nebivolol%20in%20cirrhotic%20patients%3A%20a%20pilot%20randomized%20clinical%20study.&aulast=Tarek%2C%20Mai&id=DOI:10.1038/s41598-026-56578-3 Name: Full Text Finder (for New FTF UI) (ns324271) Category: fullText Text: Full Text Finder MouseOverText: Full Text Finder |
|---|---|
| Header | DbId: edb DbLabel: Complementary Index An: 194576192 RelevancyScore: 1061 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 1060.76574707031 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Model-informed dose optimization of carvedilol and nebivolol in cirrhotic patients: a pilot randomized clinical study. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Tarek%2C+Mai%22">Tarek, Mai</searchLink><br /><searchLink fieldCode="AR" term="%22Ali%2C+Ahmed+A%22">Ali, Ahmed A</searchLink><br /><searchLink fieldCode="AR" term="%22Biomy%2C+Reda%22">Biomy, Reda</searchLink><br /><searchLink fieldCode="AR" term="%22Abdelkawy%2C+Khaled%22">Abdelkawy, Khaled</searchLink><br /><searchLink fieldCode="AR" term="%22El-Khateeb%2C+Eman%22">El-Khateeb, Eman</searchLink> – Name: TitleSource Label: Source Group: Src Data: Scientific Reports; 6/16/2026, Vol. 16 Issue 1, p1-17, 17p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Cirrhosis+of+the+liver%22">Cirrhosis of the liver</searchLink><br /><searchLink fieldCode="DE" term="%22Carvedilol%22">Carvedilol</searchLink><br /><searchLink fieldCode="DE" term="%22Portal+hypertension%22">Portal hypertension</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+research%22">Medical research</searchLink><br /><searchLink fieldCode="DE" term="%22Beta+adrenoceptors%22">Beta adrenoceptors</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacokinetics%22">Pharmacokinetics</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Liver cirrhosis causes physiological and pharmacokinetic alterations that complicate antihypertensive therapy, in the presence of portal and arterial hypertension. This study evaluated the efficacy and safety of PBPK-guided dosing of carvedilol and nebivolol in cirrhotic patients. First, PBPK models were validated using clinical pharmacokinetic data from healthy volunteers and optimized for cirrhosis, then applied to simulate untested cirrhotic populations and estimate unbound plasma exposure across disease stages. Second, a prospective, open-label, parallel randomized pilot study enrolled 44 cirrhotic patients (Child-Pugh; CP-A or B) with arterial hypertension, who received PBPK-guided doses of carvedilol or nebivolol, with 3 months of follow-up including monthly monitoring of adverse events, blood pressure, heart rate, portal hemodynamics by Doppler ultrasound, and laboratory safety parameters. The model predicted dose reductions of carvedilol 25 mg once daily and nebivolol 10 mg once daily to 11.26 mg and 4.98 mg in mild cirrhosis, 5.52 mg and 2.98 mg in moderate cirrhosis, and 1.99 mg and 1.23 mg in severe cirrhosis. Following administration of doses as close as possible to the PBPK-guided doses in CP A and B, both agents were well tolerated, effectively reducing blood pressure and heart rate without significant changes in hepatic and renal parameters. Portal hemodynamics and platelet count improved in both groups, with carvedilol showing greater effects; adverse events were mild and more frequent with carvedilol. While both drugs controlled blood pressure, carvedilol improved portal hemodynamics more. PBPK-guided dosing addressed pharmacokinetic changes, but pharmacodynamic differences between CP-A and CP-B persisted due to disease progression. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Scientific Reports is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=194576192 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/s41598-026-56578-3 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 17 StartPage: 1 Subjects: – SubjectFull: Cirrhosis of the liver Type: general – SubjectFull: Carvedilol Type: general – SubjectFull: Portal hypertension Type: general – SubjectFull: Medical research Type: general – SubjectFull: Beta adrenoceptors Type: general – SubjectFull: Pharmacokinetics Type: general Titles: – TitleFull: Model-informed dose optimization of carvedilol and nebivolol in cirrhotic patients: a pilot randomized clinical study. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Tarek, Mai – PersonEntity: Name: NameFull: Ali, Ahmed A – PersonEntity: Name: NameFull: Biomy, Reda – PersonEntity: Name: NameFull: Abdelkawy, Khaled – PersonEntity: Name: NameFull: El-Khateeb, Eman IsPartOfRelationships: – BibEntity: Dates: – D: 16 M: 06 Text: 6/16/2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 20452322 Numbering: – Type: volume Value: 16 – Type: issue Value: 1 Titles: – TitleFull: Scientific Reports Type: main |
| ResultId | 1 |