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NCT Number: NCT03612180

Evaluation of Metoprolol Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis

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.

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Key information

Conditions

Hemodialysis Pharmacokinetics

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Michigan Dialysis

Ann Arbor, Michigan, 48109, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Metoprolol succinate

Drug

Pharmacokinetics

Primary outcomes

  1. Plasma pharmacokinetics-Maximal Plasma Concentration

    Time frame: 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

  2. Plasma pharmacokinetics-Time to Maximal Plasma Concentration

    Time frame: 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

  3. Plasma Pharmacokinetics-Area under the concentration time curve (AUC)

    Time frame: 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

  4. Plasma Pharmacokinetics-Clearance

    Time frame: 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

  5. Plasma Pharmacokinetics-Volume of Distribution

    Time frame: 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

  6. Plasma Pharmacokinetics-elimination rate constant

    Time frame: 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

  7. Plasma Pharmacokinetics-half-life

    Time frame: 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 outcomes

  1. Non-renal clearance phenotype and genotype

    Time frame: 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

  2. Post-dialysis Rebound

    Time frame: post-dialysis (30 minutes, 2 hours and 4 hours)

    Simulate predicted rebound of metoprolol concentrations

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Registry information

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Aug 2, 2018
Registry last updated
Jul 29, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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