Evaluation of Amlodipine Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/17/2019 |
| Start Date: | December 2019 |
| End Date: | January 30, 2020 |
| Contact: | Amy Pai, PharmD |
| Email: | amypai@med.umich.edu |
| Phone: | 7346470005 |
The current study will evaluate the plasma pharmacokinetics of amlodipine 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 5-10 mg of amlodipine besylate for
>30 days as part of their usual care. Blood sampling will occur over 13 hours, with frequent
sampling during HD and in the 4 hours after termination of HD treatment. The 8 subjects will
all receive their prescribed total daily dose of 5-10 mg 5 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 CYP3A4. CYP3A4 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 amlodipine
clearance. Monte Carlo simulations will be performed to compare amlodipine 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 5-10 mg of amlodipine besylate for
>30 days as part of their usual care. Blood sampling will occur over 13 hours, with frequent
sampling during HD and in the 4 hours after termination of HD treatment. The 8 subjects will
all receive their prescribed total daily dose of 5-10 mg 5 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 CYP3A4. CYP3A4 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 amlodipine
clearance. Monte Carlo simulations will be performed to compare amlodipine pharmacokinetic
profiles on and off HD.
Inclusion Criteria:
1. 18 years of age or older
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 5-10 mg of amlodipine 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 CYP3A4 inhibitor (most common in HD population include: amiodarone,
clarithromycin, cyclosporine, diltiazem, erythromycin, fluconazole, fluoxetine,
fluvoxamine, nefazodone, tamoxifen, verapamil, and grapefruit juice).
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