1: J Pharm Sci  2001 Nov;90(11):1897-906

Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of
flurbiprofen in the rat.

Mathy FX, Preat V, Verbeeck RK.

Universite Catholique de Louvain, Unite de Pharmacie Galenique, Industrielle et
Officinale, 7320, 1200 Brussels, Belgium.

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. Copyright 2001 Wiley-Liss, Inc. and
the American Pharmaceutical Association

PMID: 11745747 [PubMed - in process]