What is the clinical evidence from this study?

Study design: Observational. Population: Septic shock with persistent tachycardia requiring renal replacement therapy (n=6). Intervention: Landiolol. Primary outcome: Dialytic clearance of landiolol (mL/min).

April 3, 2026European Journal of Drug Metabolism and Pharmacokinetics0 citationsOpen Access

Pharmacokinetics of Landiolol and Its Metabolite M1 During Renal Replacement Therapy in Septic Shock Patients: A Sub-Study of the Landi-SEP Trial

SRSebastian RehbergCARE USA RBRainer BorgstedtEvangelisches Krankenhaus Bielefeld SFSandra FrankStevens Institute of Technology

Key Result

Landiolol clearance was minimally affected by dialysis (2.4% of total clearance), while a substantial proportion (50.9%) of its metabolite M1 was removed during renal replacement therapy.

Key Points

To evaluate the pharmacokinetics and dialytic clearance of landiolol and its metabolite M1 in septic shock patients undergoing renal replacement therapy.
Conducted as a sub-study within the Landi-SEP trial
Included septic shock patients receiving renal replacement therapy
Measured pharmacokinetic parameters including clearance and area under curve
Assessed pharmacodynamic data such as heart rate and blood pressure
Mean dialytic clearance was 39.3 mL/min for landiolol and 42.3 mL/min for M1
Dialysis accounted for 2.4% of total landiolol clearance and 50.9% of M1 clearance
Heart rate and blood pressure remained stable during the study
No reports of hypotension or bradycardia were noted
Findings support existing dosing recommendations for renal impairment

Study Design

Type

Observational (n=6)

Blinding

Open-label

Multicenter

Yes

Structured PICO

Population

6 adult patients with septic shock and persistent tachycardia (HR ≥ 95 bpm) undergoing renal replacement therapy (RRT), mean age 62.7, 50% male, multinational (Germany, Czech Republic).

Intervention

Landiolol continuous infusion (starting at 1 µg/kg/min, progressively increased up to a maximum of 40 µg/kg/min to achieve target HR of 80-94 bpm) added to standard care.

Outcome

Pharmacokinetic parameters, including dialytic and total clearance and area under the concentration–time curve (AUC) of landiolol and its metabolite M1 over 8 hours.surrogate

Dialysis has minimal impact on landiolol clearance but removes a substantial proportion of its metabolite M1, suggesting no dose adjustment is required during renal replacement therapy.

Limitations

Small number of participants (n=6)
Sparse sampling points leading to potential inaccuracies in AUC calculation
Absence of PK samples collected after discontinuation of landiolol, precluding elimination half-life calculation
Variations in RRT settings and adjustments to dialysis/filtration parameters during the study
Fluctuations in landiolol dosing throughout the study period

Abstract

Landiolol, an ultra-short-acting β-blocker, is commonly used to manage tachyarrhythmias, including critically ill patients requiring renal replacement therapy (RRT). Pharmacokinetic (PK) data for landiolol in these patients are lacking. This study aimed to evaluate the PK and dialytic clearance of landiolol and its metabolite, M1, in septic shock patients receiving RRT, with the goal of guiding dosing optimization to ensure safe and effective treatment in this high-risk population. This pre-defined PK sub-study was embedded within the Landi-SEP trial, which randomized patients with septic shock and persistent tachycardia to receive standard care or standard care with landiolol. Patients from two centers undergoing RRT were included in the sub-study. PK parameters, including dialytic and total clearance and area under the concentration–time curve (AUC), were determined based on plasma concentrations of landiolol and M1. Pharmacodynamic data, including heart rate (HR) and blood pressure (BP), were assessed concurrently. Six patients were included in the final analysis. Mean dialytic clearance was 39.3 mL/min for landiolol and 42.3 mL/min for M1. Dialysis accounted for 2.4% of total landiolol clearance and 50.9% of M1 clearance. HR and BP remained stable throughout the sub-study and no adverse events related to hypotension or bradycardia were reported. Dialysis minimally affected landiolol clearance but removed a substantial proportion of M1. These exploratory data align with current dosing recommendations in patients with renal impairment and suggest that no dose adjustment is required during RRT. Individualized dosing and hemodynamic monitoring remain essential. EU Clinical Trial Register; EudraCT Number: 2017-002138-22

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