Kratzer, Alexander and Kees, Frieder and Dorn, Christoph (2016) Unbound fraction of fluconazole and linezolid in human plasma as determined by ultrafiltration: Impact of membrane type. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 1039. pp. 74-78. ISSN 1570-0232, 1873-376X
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Ultrafiltration is a rapid and convenient method to determine the free concentrations of drugs in plasma. Several ultrafiltration devices based on Eppendorf cups are commercially available, but are not validated for such use by the manufacturer. Plasma pH, temperature and relative centrifugal force as well as membrane type can influence the results. In the present work, we developed an ultrafiltration method in order to determine the free concentrations of linezolid or fluconazole, both neutral and moderately lipophilic antiinfective drugs for parenteral as well as oral administration, in plasma of patients. Whereas both substances behaved relatively insensitive in human plasma regarding variations in pH (7.0-8.5), temperature (5-37 degrees C) or relative centrifugal force (1000-10.000 xg), losses of linezolid were observed with the Nanosep Omega device due to adsorption onto the polyethersulfone membrane (unbound fraction 75% at 100 mg/L and 45% at 0.1 mg/L, respectively). No losses were observed with Vivacon which is equipped with a membrane of regenerated cellulose. With fluconazole no differences between Nanosep and Viva con were observed. Applying standard conditions (pH 7.4/37 degrees C/1000 xg/20 min), the mean unbound fraction of linezolid in pooled plasma from healthy volunteers was 81.5 +/- 2.8% using Vivacon, that of fluconazole was 87.9 +/- 3.5% using Nanosep or 89.4 +/- 3.3% using Vivacon. The unbound fraction of linezolid was 85.4 +/- 3.7% in plasma samples from surgical patients and 92.1 +/- 6.2% in ICU patients, respectively. The unbound fraction of fluconazole was 93.9 +/- 3.3% in plasma samples from ICU patients. (C) 2016 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CRITICALLY-ILL PATIENTS; PROTEIN-BINDING; DRUGS; PHARMACOKINETICS; PH; MICRODIALYSIS; VANCOMYCIN; DOCETAXEL; HPLC; Antiinfectives; Protein binding; Patients; Polyethersulfone; Regenerated cellulose |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2019 13:56 |
| Last Modified: | 08 Apr 2019 13:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3781 |
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