Evaluation of Metoprolol Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis
| Status: | Recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 8/4/2018 |
| Start Date: | June 30, 2018 |
| End Date: | May 31, 2019 |
| Contact: | Amy Pai, PharmD |
| Email: | amypai@med.umich.edu |
| Phone: | 7346470005 |
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.
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.
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)
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