Focus of the Study:Protein Binding Characteristics of Voriconazole.
Conditions
Keywords
protein binding, voriconazole, pediatrics, hematology, intensive care, albumin, alpha-1-acid-glycoprotein
Brief summary
The purpose of this study is to investigate the influence of hypoalbuminemia on the protein binding characteristics of the antifungal drug voriconazole in ICU patients.
Interventions
OTHERBlood sampling
During the treatment of voriconazole, at steady plasma concentrations of voriconazole, one plasma sample and one serum sample are taken.
Sponsors
Universitaire Ziekenhuizen KU Leuven
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* treated with voriconazole
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in Overall Protein Binding in the Presence of Different Plasma Albumin Concentrations. | At steady state plasma concentration of voriconazole (after day 4 of therapy) | At steady state plasma concentrations of voriconazole, a plasma sample is taken to determine the overall protein binding of voriconazole. Equilibrium dialysis is used, followed by liquid chromatography-mass spectrometry. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients Admitted Tot the ICU Not Treated With Voriconazole Patients admitted to the intensive Care Unit, with varying levels of plasma albumin concentrations during admission.
Plasma from this patients will be spiked in vitro with different voriconazole concentrations to investigate the influence of low albumine concentrations in plasma on voriconazole protein binding characteristics. | 22 |
| Patients Admitted to the ICU Treated With Voriconazole Patients admitted to the Intensive Care Unit, treated with voriconazole are included in this study. Voriconazole protein binding will be determined and the correlation with albumin plasma concentrations will be evaluated. | 13 |
| Total | 35 |
Baseline characteristics
| Characteristic | Patients Admitted Tot the ICU Not Treated With Voriconazole | Total | Patients Admitted to the ICU Treated With Voriconazole |
|---|---|---|---|
| Acute Physiology and Chronic Health Evaluation (Apache) score | 23.5 units of the Apache Scoring system STANDARD_DEVIATION 10 | 25.3 units of the Apache Scoring system STANDARD_DEVIATION 8.3 | 26.8 units of the Apache Scoring system STANDARD_DEVIATION 6.9 |
| Age, Continuous | 66 years | 65 years | 62 years |
| Albumin plasma concentration | 23.7 gram/liter | 26.7 gram/liter | 31.1 gram/liter |
| alfa-1-acid glycoprotein plasma concentration | 1.4 gram/liter | 1.5 gram/liter | 1.8 gram/liter |
| Blood Urea Nitrogen | 54.5 milligram/deciliter | 57.5 milligram/deciliter | 70 milligram/deciliter |
| Body weight | 71 kilogram | 68 kilogram | 68 kilogram |
| Bound voriconazole plasma concentration | 1.63 milligram / liter | 1.62 milligram / liter | 1.52 milligram / liter |
| C reactive protein plasma concentration | 72.1 milligram/liter | 71.5 milligram/liter | 47.2 milligram/liter |
| Creatinin plasma concentration | 1.14 milligram/deciliter | 1.13 milligram/deciliter | 0.95 milligram/deciliter |
| estimated Glomerular Filtration Rate (CKD-EPI equation) | 66 ml/min * 1.73m² | 74 ml/min * 1.73m² | 84 ml/min * 1.73m² |
| Number of coadministered drugs bound to proteins for more then 70% | 4.5 number of coadministered drugs | 3 number of coadministered drugs | 2.5 number of coadministered drugs |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Male | 14 Participants | 21 Participants | 7 Participants |
| Total plasma bilirubin concentration | 0.75 milligram/liter | 0.67 milligram/liter | 0.41 milligram/liter |
| Total plasma protein concentration | 53.4 gram/liter STANDARD_DEVIATION 12.4 | 54.2 gram/liter STANDARD_DEVIATION 11.5 | 56.6 gram/liter STANDARD_DEVIATION 7.3 |
| Total voriconazole plasma concentration | NA milligram/liter | 2.9 milligram/liter | 2.4 milligram/liter |
| Unbound voriconazole plasma concentration | 0.86 milligram/liter | 0.85 milligram/liter | 0.71 milligram/liter |
| Voriconazole daily dose | NA milligram/kilogram/day | NA milligram/kilogram/day | 8 milligram/kilogram/day |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 22 | 0 / 13 |
| serious Total, serious adverse events | 0 / 22 | 0 / 13 |
Outcome results
Primary
Differences in Overall Protein Binding in the Presence of Different Plasma Albumin Concentrations.
At steady state plasma concentrations of voriconazole, a plasma sample is taken to determine the overall protein binding of voriconazole. Equilibrium dialysis is used, followed by liquid chromatography-mass spectrometry.
Time frame: At steady state plasma concentration of voriconazole (after day 4 of therapy)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients Admitted Tot the ICU Not Treated With Voriconazole | Differences in Overall Protein Binding in the Presence of Different Plasma Albumin Concentrations. | 49.1 % of plasma protein binding |
| Patients Admitted to the ICU Treated With Voriconazole | Differences in Overall Protein Binding in the Presence of Different Plasma Albumin Concentrations. | 49.6 % of plasma protein binding |