Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis.

Stark JG, Noonan PK, Spencer RH, Bhaduri S, O'Connor SJ, Menzaghi F

Clinical pharmacokinetics28 Jun 2023Cited by 9 (Europe PMC)

PMID37369955PMCIDPMC10450003DOI10.1007/s40262-023-01262-2PepBankPUB-37369955

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: CC BY-NC. Results still quote short attributed sentences.

Results from this study10

10 results from studies that gave the peptide. 10 results from people.

01HumanNon-randomized trialPharmacokinetics
In men receiving difelikefalin, median time to maximum concentration was similar in hemodialysis and healthy subjects, at 5 min.
In plain wordsIn men, median time to peak difelikefalin concentration was 5 minutes in both healthy and hemodialysis groups.
Peptide
Difelikefalin
Outcome
Direction not reportedTime to maximum concentration
Study
n = 12
Comparator
Healthy subjects
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Median time to maximum concentration
5 min
HD and healthy subjects, post-dose
Source sentences
Summary
The median time to maximum concentration was similar for HD and healthy subjects, occurring at 5 min post-dose.
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995501
02HumanNon-randomized trialPharmacokinetics
In men, difelikefalin mean AUC was approximately 11-fold higher in hemodialysis than healthy subjects.
In plain wordsIn men receiving hemodialysis, difelikefalin exposure was approximately 11-fold higher than in healthy men.
Peptide
Difelikefalin
Outcome
IncreasePlasma AUC
Study
n = 12
Comparator
Healthy subjects
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Mean AUC ratio, HD versus healthy subjects
≈ 11 fold
HD versus healthy subjects
Source sentences
Summary
The mean area under the concentration-time curve (AUC) was approximately 11-fold higher in HD versus healthy subjects; mean plasma half-life was 38.0 h and 2.6 h, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995502
03HumanNon-randomized trialPharmacokinetics
In men, difelikefalin mean plasma half-life was 38.0 h with hemodialysis versus 2.6 h in healthy subjects.
In plain wordsIn men receiving hemodialysis, difelikefalin half-life was 38.0 hours versus 2.6 hours in healthy men.
Peptide
Difelikefalin
Outcome
IncreasePlasma half-life
Study
n = 12
Comparator
Healthy subjects
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Mean plasma half-life
38 h
subjects on HD
Mean plasma half-life
2.6 h
healthy subjects
Source sentences
Summary
The mean area under the concentration-time curve (AUC) was approximately 11-fold higher in HD versus healthy subjects; mean plasma half-life was 38.0 h and 2.6 h, respectively.
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995503
04HumanNon-randomized trialPharmacokinetics
In healthy men and men on hemodialysis, parent difelikefalin represented >99% of total systemic exposure based on plasma AUC.
In plain wordsIn healthy men and men on hemodialysis, unchanged difelikefalin represented >99% of total exposure.
Peptide
Difelikefalin
Outcome
Not applicableUnchanged parent systemic exposure
Study
n = 12
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Parent difelikefalin share of total systemic exposure (plasma AUClast)
> 99 % of total exposure
both cohorts
Source sentences
Summary
Based on plasma AUC_last, parent [¹⁴C]difelikefalin was the most abundant analyte in systemic circulation (> 99% of total exposure) for both cohorts.
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995509
05HumanNon-randomized trialPharmacokinetics
In healthy men and men on hemodialysis, urine and fecal profiles suggested minimal difelikefalin metabolism.
In plain wordsIn healthy men and men on hemodialysis, sample profiles suggested minimal breakdown of difelikefalin.
Peptide
Difelikefalin
Outcome
Not applicableMetabolism
Study
n = 12
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Source sentences
Summary
Metabolite profiles in urine and feces suggested minimal metabolism of the parent compound.
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995510
06HumanNon-randomized trialPharmacokinetics
In healthy men, urine contained 80.5% of the administered difelikefalin dose.
In plain wordsIn healthy men, urine contained 80.5% of the difelikefalin dose.
Peptide
Difelikefalin
Outcome
Not applicableUrinary dose recovery in healthy subjects
Study
n = 6
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Dose recovered in urine
80.5%
healthy subjects
Source sentences
Summary
In healthy subjects, 80.5% of the dose was recovered in urine, and 11.3% was recovered in feces.
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995504
07HumanNon-randomized trialPharmacokinetics
In healthy men, feces contained 11.3% of the administered difelikefalin dose.
In plain wordsIn healthy men, feces contained 11.3% of the difelikefalin dose.
Peptide
Difelikefalin
Outcome
Not applicableFecal dose recovery in healthy subjects
Study
n = 6
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Dose recovered in feces
11.3%
healthy subjects
Source sentences
Summary
In healthy subjects, 80.5% of the dose was recovered in urine, and 11.3% was recovered in feces.
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995505
08HumanNon-randomized trialPharmacokinetics
In men on hemodialysis, feces contained 58.8% of the administered difelikefalin dose.
In plain wordsIn men on hemodialysis, feces contained 58.8% of the difelikefalin dose.
Peptide
Difelikefalin
Outcome
Not applicableFecal dose recovery in hemodialysis subjects
Study
n = 6
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Dose recovered in feces
58.8%
subjects on HD
Source sentences
Summary
In subjects on HD, 58.8% of the dose was recovered in feces, and 19.5% was recovered in dialysate [for subjects on HD with residual kidney function (n = 3), 11.2% was recovered in urine].
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995506
09HumanNon-randomized trialPharmacokinetics
In men on hemodialysis, dialysate contained 19.5% of the administered difelikefalin dose.
In plain wordsIn men on hemodialysis, dialysate contained 19.5% of the difelikefalin dose.
Peptide
Difelikefalin
Outcome
Not applicableDialysate dose recovery
Study
n = 6
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Dose recovered in dialysate
19.5%
subjects on HD
Source sentences
Summary
In subjects on HD, 58.8% of the dose was recovered in feces, and 19.5% was recovered in dialysate [for subjects on HD with residual kidney function (n = 3), 11.2% was recovered in urine].
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995507
10HumanNon-randomized trialPharmacokinetics
In men on hemodialysis with residual kidney function, urine contained 11.2% of the administered difelikefalin dose.
In plain wordsIn men on hemodialysis with residual kidney function, urine contained 11.2% of the difelikefalin dose.
Peptide
Difelikefalin
Outcome
Not applicableUrinary dose recovery with residual kidney function
Study
n = 3
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
1.7-3.0 μg/kg · intravenous · single doseAs given in this study (human).
Measurements
Dose recovered in urine
11.2%
subjects on HD with residual kidney function (n = 3)
Source sentences
Summary
In subjects on HD, 58.8% of the dose was recovered in feces, and 19.5% was recovered in dialysate [for subjects on HD with residual kidney function (n = 3), 11.2% was recovered in urine].
2 context sentences(design, population, supporting numbers)
Summary · context
The purpose of this open-label study was to investigate the pharmacokinetics and disposition of [¹⁴C]difelikefalin following a single intravenous dose in subjects with normal renal function and subjects on HD.
Summary · context
Twelve adult males (n = 6 healthy subjects; n = 6 subjects on HD) received single intravenous doses of [¹⁴C]difelikefalin containing 100 µCi (total doses of 1.7-3.0 μg/kg difelikefalin).
Report a problemFND-3736995508

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 1NCT03947970

Study to Evaluate the Pharmacokinetics and Metabolism of [14C] CR845 (Difelikefalin) in Patients With End Stage Renal Disease on Hemodialysis and in Healthy Subjects

Cara Therapeutics, Inc.n = 1217 Jan 2019 to 6 Apr 2019

Hemodialysis · Healthy

Trial page ClinicalTrials.govUpdated 24 Jul 2019

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:35 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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