Clinical Application of Simcyp-Guided Doses of Antihypertensive Drugs in Cirrhotic Patients

Summary

This was a prospective, open-label, randomized, parallel pilot clinical study conducted over 3 months on 50 Egyptian cirrhotic patients with arterial hypertension and portal hypertension, evaluating the real-world applicability of selected PBPK-guided dosing regimens. Patients were stratified according to Child-Pugh class (CP-A or CP-B) and randomly assigned to receive either nebivolol or carvedilol at doses corresponding to the closest commercially available strengths to Simcyp®-predicted doses.

Clinical evaluation included serial blood pressure measurements, comprising systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR). Doppler ultrasonographical assessment was performed to evaluate portal and hepatic hemodynamics, including portal vein diameter, portal vein velocity, congestion index, hepatic artery resistive index, and modified vascular liver index. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase \[ALT\], and aspartate aminotransferase \[AST\]), kidney function tests (serum creatinine and blood urea nitrogen \[BUN\]), and fasting blood glucose. Patients were followed on a monthly basis, with systematic documentation of adverse events throughout the study period.

Conditions

• Liver Cirrhosis
• Arterial Hypertension

Interventions

DRUG

Nebivolol 5 mg

Nebivolol is a third-generation cardio-selective β-1 adrenergic blocker with nitric oxide-mediated vasodilatory properties and it is primarily used to treat hypertension . Nebivolol reduces intrahepatic vascular resistance by enhancing nitric oxide (NO) production within the hepatic endothelium, thereby lowering portal pressure.

DRUG

Carvedilol 12.5 mg

Carvedilol is used to treat hypertension and it lowers blood pressure effectively through a combination of β adrenergic blockade and α-1-mediated vasodilation. Carvedilol lowers portal pressure by β1-mediated reduction of cardiac output, β2-mediated splanchnic vasoconstriction, and additional α1-adrenergic blockade, which induces intrahepatic vasodilation, thereby reducing portal hypertension.

DRUG

Nebivolol 2.5 mg

Nebivolol is a third-generation cardio-selective β-1 adrenergic blocker with nitric oxide-mediated vasodilatory properties and it is primarily used to treat hypertension . Nebivolol reduces intrahepatic vascular resistance by enhancing nitric oxide (NO) production within the hepatic endothelium, thereby lowering portal pressure.

DRUG

Carvedilol 6.25 mg

Carvedilol is used to treat hypertension and it lowers blood pressure effectively through a combination of β adrenergic blockade and α-1-mediated vasodilation. Carvedilol lowers portal pressure by β1-mediated reduction of cardiac output, β2-mediated splanchnic vasoconstriction, and additional α1-adrenergic blockade, which induces intrahepatic vasodilation, thereby reducing portal hypertension.

Sponsors & Collaborators

• Kafrelsheikh University

  lead OTHER

Principal Investigators

• Mai Tarek Hamed, BSc (Pharmacy) · Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

• Ahmed A Ali, PhD · Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-01

Primary Completion

2025-03-01

Completion

2025-06-01

Countries

• Egypt

Study Locations