Evaluation of Metoprolol Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis

Pharmacokinetics Clinical Trial

Official title:

Evaluation of Metoprolol Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03612180
• Other study ID #: HUM00138192
• Status: Completed
• Start date: June 30, 2018
• Est. completion date: May 31, 2019

Study information

• Verified date: July 2019
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: May 31, 2019
• Est. primary completion date: May 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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)

Related Conditions & MeSH terms

• Hemodialysis
• Pharmacokinetics

Intervention

Drug:
• Metoprolol Succinate
Pharmacokinetics

Locations

Country	Name	City	State
United States	University of Michigan Dialysis	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma pharmacokinetics-Maximal Plasma Concentration	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Primary	Plasma pharmacokinetics-Time to Maximal Plasma Concentration	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Primary	Plasma Pharmacokinetics-Area under the concentration time curve (AUC)	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Primary	Plasma Pharmacokinetics-Clearance	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Primary	Plasma Pharmacokinetics-Volume of Distribution	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Primary	Plasma Pharmacokinetics-elimination rate constant	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Primary	Plasma Pharmacokinetics-half-life	Characterize the pharmacokinetics of metoprolol and its metabolite, alpha-hydroxymetoprolol during and after HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Secondary	Non-renal clearance phenotype and genotype	Evaluate the non-renal clearance of metoprolol in patients on HD	Pre-dialysis, during dialysis (30 minutes, 2 hours, end of treatment) and post-dialysis (30 minutes, 2 hours and 4 hours)
Secondary	Post-dialysis Rebound	Simulate predicted rebound of metoprolol concentrations	post-dialysis (30 minutes, 2 hours and 4 hours)