Evaluation of Metoprolol Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis

Completed

• Conditions: Hemodialysis; Pharmacokinetics

• Registration Number: NCT03612180
• Lead Sponsor: University of Michigan

Brief Summary

The current study will evaluate the plasma pharmacokinetics of metoprolol in a cohort of 8 adult volunteers who are receiving regular hemodialysis treatment (HD) 3 days a week for 4 hours each day and have been taking a total daily dose of 25-200 mg of metoprolol succinate for \>30 days as part of their usual care. Blood sampling will occur over 10 hours, with frequent sampling during HD and in the 4 hours after termination of HD treatment. The 8 subjects will all receive their prescribed dose (25-200 mg total daily dose) 2 hours prior to HD treatment. The pre-HD sample will also be sent for pharmacogenomics genotyping. Safety and pharmacodynamic assessments (blood pressure (BP) and heart rate (HR) assessments) will be performed throughout the study. Axiom Precision Medicine Research Array (Affymetrix, Santa Clara, CA) will be used to evaluate genotype of CYP2D6. CYP2D6 phenotype will be evaluated using the ratio of parent drug to metabolite. Non-compartmental analyses will be performed to compare maximum concentrations (Cmax), time to maximum concentration and area under the curve from time 0 to the last measurable sample (AUClast) between the two phases. Compartmental analyses will be performed to construct a model to explain time-dependent changes in metoprolol clearance. Monte Carlo simulations will be performed to compare metoprolol pharmacokinetic profiles on and off HD.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-30
• Study First Submitted: 2018-07-12
• Study First Submitted QC: 2018-08-01
• Study First Posted: 2018-08-02
• Primary Completion: 2019-05-31
• Study Completion: 2019-05-31
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-25
• Last Update Posted: 2019-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. Age > 18 years
2. Indwelling tunneled catheter, AVF, AVG that is currently used for hemodialysis
3. Receiving in-center hemodialysis 3 days a week for 3-4.5 hours each treatment
4. Taking a total daily dose of 25-200 mg metoprolol succinate as prescribed by their physician
5. Hemoglobin ≥ 9.5 g/dL on most recent laboratory assessment prior to study

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Exclusion Criteria

1. Any condition that would not allow for arm BP to be taken
2. Hemoglobin < 9.5 g/dL on most recent lab prior to study
3. Patient is on a CYP2D6 inhibitor (most common in HD population amiodarone, bupropion, cinacalcet, diphenhydramine, fluoxetine, paroxetine)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Plasma pharmacokinetics-Maximal Plasma Concentration	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD
Plasma pharmacokinetics-Time to Maximal Plasma Concentration	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD
Plasma Pharmacokinetics-Area under the concentration time curve (AUC)	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD
Plasma Pharmacokinetics-half-life	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD
Plasma Pharmacokinetics-Clearance	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD
Plasma Pharmacokinetics-elimination rate constant	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD
Plasma Pharmacokinetics-Volume of Distribution	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD

Secondary Outcome Measures

Name	Time	Method
Non-renal clearance phenotype and genotype	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)	Evaluate the non-renal clearance of metoprolol in patients on HD
Post-dialysis Rebound	post-dialysis (30 minutes, 2 hours and 4 hours)	Simulate predicted rebound of metoprolol concentrations

Trial Locations

Locations (1)

University of Michigan Dialysis; 🇺🇸 Ann Arbor, Michigan, United States