PMID- 11745747
OWN - NLM
STAT- MEDLINE
DCOM- 20020304
LR  - 20191210
IS  - 0022-3549 (Print)
IS  - 0022-3549 (Linking)
VI  - 90
IP  - 11
DP  - 2001 Nov
TI  - Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of 
      flurbiprofen in the rat.
PG  - 1897-906
AB  - The objective of this study was to validate subcutaneous (sc) microdialysis 
      sampling to study flurbiprofen pharmacokinetics and plasma protein binding in the 
      awake freely moving rat. A linear microdialysis probe was manufactured using a 
      Hemophane hollow fiber which was tested in vitro and in vivo for the recovery of 
      flurbiprofen and naproxen used as retrodialysis marker. Flurbiprofen was 
      administered intraperitoneally and intravenously at a dose of 20 mg/kg in rats. 
      In both cases, conventional blood sampling and sc microdialysis sampling were 
      simultaneously performed. The microdialysates were analyzed on-line by 
      high-pressure liquid chromatography. Naproxen, which was shown to have a similar 
      in vivo loss by retrodialysis as flurbiprofen (71.5 +/- 0.9% and 71.0 +/- 0.8% 
      respectively, n = 3), was used to continuously monitor probe recovery. 
      Concentration-dependent protein binding of flurbiprofen was demonstrated in vivo 
      based on experiments with a simultaneous sc microdialysis and blood sampling. 
      Values of unbound fraction were similar to those reported previously by 
      intravenous microdialysis sampling, demonstrating that the sc unbound 
      concentrations are very similar to those in the central compartment. There was no 
      significant difference among pharmacokinetic parameters (AUC, CL, t(1/2z), Vd) 
      for total or unbound flurbiprofen determined after intraperitoneal and 
      intravenous administration. Subcutaneous microdialysis is a simple yet powerful 
      tool to study the pharmacokinetics and the in vivo plasma protein binding of 
      flurbiprofen in the awake unrestrained rat.
CI  - Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association
FAU - Mathy, F X
AU  - Mathy FX
AD  - Universite Catholique de Louvain, Unite de Pharmacie Galenique, Industrielle et 
      Officinale, 7320, 1200 Brussels, Belgium.
FAU - Preat, V
AU  - Preat V
FAU - Verbeeck, R K
AU  - Verbeeck RK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Blood Proteins)
RN  - 5GRO578KLP (Flurbiprofen)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacokinetics
MH  - Blood Proteins/pharmacokinetics
MH  - Flurbiprofen/*pharmacokinetics
MH  - Injections, Intraperitoneal
MH  - Injections, Intravenous
MH  - Male
MH  - Microdialysis/*methods
MH  - Protein Binding
MH  - Rats
EDAT- 2001/12/18 10:00
MHDA- 2002/03/05 10:01
CRDT- 2001/12/18 10:00
PHST- 2001/12/18 10:00 [pubmed]
PHST- 2002/03/05 10:01 [medline]
PHST- 2001/12/18 10:00 [entrez]
AID - 10.1002/jps.1139 [pii]
AID - 10.1002/jps.1139 [doi]
PST - ppublish
SO  - J Pharm Sci. 2001 Nov;90(11):1897-906. doi: 10.1002/jps.1139.