Small volume rapid equilibrium dialysis (RED) measures effects of interstitial parameters on the protein-bound fraction of topical drugs
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
The importance of plasma protein binding in the early stages of drug development is well recognized. Free and bound drug fractions in plasma are routinely determined with well-established methods. However, for physiological fluids with a small accessible volume and low protein concentrations, such as dermal interstitial fluid (dISF) validated methods are currently missing. Due to the low protein concentration and highly dynamic processes in the dermis, protein binding data obtained from plasma samples may underestimate in-vivo efficacy. This study aimed to validate a small volume rapid equilibrium dialysis (RED) for low protein samples, as a tool to examine drug-protein binding directly in the biological fluid at the site of action. The sample volume required for RED was successfully downscaled to 50 µl and plasma protein binding values of the four model drugs were consistent with previous studies with an average recovery of 88 ± 8% which makes all tested drugs suitable for small volume RED. Inter- and intra-batch variability showed sufficient reproducibility across RED plates. Small volume RED was successfully applied to assess the effects of interstitial parameters, including the evaluation of the major binding protein and the effects of binding protein concentration, drug concentration, and pH on the protein-bound drug fraction using 2% HSA and/or diluted human plasma as a surrogate for dISF.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:234 |
---|---|
Enthalten in: |
Journal of pharmaceutical and biomedical analysis - 234(2023) vom: 20. Sept., Seite 115571 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Wiltschko, Laura [VerfasserIn] |
---|
Links: |
---|
Themen: |
Albumin |
---|
Anmerkungen: |
Date Completed 28.08.2023 Date Revised 28.08.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.jpba.2023.115571 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM360273947 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM360273947 | ||
003 | DE-627 | ||
005 | 20231226082650.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.jpba.2023.115571 |2 doi | |
028 | 5 | 2 | |a pubmed24n1200.xml |
035 | |a (DE-627)NLM360273947 | ||
035 | |a (NLM)37527618 | ||
035 | |a (PII)S0731-7085(23)00340-0 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Wiltschko, Laura |e verfasserin |4 aut | |
245 | 1 | 0 | |a Small volume rapid equilibrium dialysis (RED) measures effects of interstitial parameters on the protein-bound fraction of topical drugs |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 28.08.2023 | ||
500 | |a Date Revised 28.08.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
520 | |a The importance of plasma protein binding in the early stages of drug development is well recognized. Free and bound drug fractions in plasma are routinely determined with well-established methods. However, for physiological fluids with a small accessible volume and low protein concentrations, such as dermal interstitial fluid (dISF) validated methods are currently missing. Due to the low protein concentration and highly dynamic processes in the dermis, protein binding data obtained from plasma samples may underestimate in-vivo efficacy. This study aimed to validate a small volume rapid equilibrium dialysis (RED) for low protein samples, as a tool to examine drug-protein binding directly in the biological fluid at the site of action. The sample volume required for RED was successfully downscaled to 50 µl and plasma protein binding values of the four model drugs were consistent with previous studies with an average recovery of 88 ± 8% which makes all tested drugs suitable for small volume RED. Inter- and intra-batch variability showed sufficient reproducibility across RED plates. Small volume RED was successfully applied to assess the effects of interstitial parameters, including the evaluation of the major binding protein and the effects of binding protein concentration, drug concentration, and pH on the protein-bound drug fraction using 2% HSA and/or diluted human plasma as a surrogate for dISF | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Albumin | |
650 | 4 | |a Alpha 1-acid glycoprotein | |
650 | 4 | |a HPLC-MS | |
650 | 4 | |a Interstitial fluid | |
650 | 4 | |a Protein binding | |
650 | 4 | |a Rapid equilibrium dialysis | |
650 | 7 | |a Blood Proteins |2 NLM | |
700 | 1 | |a Roblegg, Eva |e verfasserin |4 aut | |
700 | 1 | |a Raml, Reingard |e verfasserin |4 aut | |
700 | 1 | |a Birngruber, Thomas |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Journal of pharmaceutical and biomedical analysis |d 1983 |g 234(2023) vom: 20. Sept., Seite 115571 |w (DE-627)NLM012641928 |x 1873-264X |7 nnns |
773 | 1 | 8 | |g volume:234 |g year:2023 |g day:20 |g month:09 |g pages:115571 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jpba.2023.115571 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 234 |j 2023 |b 20 |c 09 |h 115571 |