Evrard-PA; Cumps-J; Verbeeck-RK
Pharm-Res. 1996 Jan; 13(1): 18-22
PURPOSE. The in vivo plasma protein binding and pharmacokinetics of
flurbiprofen were studied in awake, unrestrained rats using intravenous
microdialysis sampling.
METHODS. Flurbiprofen (20 mg/kg) was administered i.v. to 2 groups
of 6 rats: in both groups sampling was carried out by microdialysis, but
in the second group an additional 10 blood samples were withdrawn via a
jugular cannula. In vitro and ex vivo (following i.v. administration of
flurbiprofen 20 mg/kg to another group of 13 rats) plasma protein binding
of the drug was determined by equilibrium dialysis.
RESULTS. The area under the unbound plasma concentration-time profile
of flurbiprofen (AUCu), determined by microdialysis sampling was somewhat
smaller (-19%, p = 0.666) in the rats undergoing simultaneous serial blood
sampling (2.21 +/- 0.36 micrograms.h/ml) as compared to the rats undergoing
microdialysis sampling only (2.73 +/- 0.60 micrograms.h/ml). Comparison
of total and unbound concentrations of flurbiprofen showed an in vivo plasma
binding varying between 99.5% at low and 98.0% at high total flurbiprofen
plasma concentrations. Plasma binding of flurbiprofen determined in vitro
over the same concentration range was higher (99.5-99.9%) but also concentration-dependent.
Plasma binding of flurbiprofen determined ex vivo, on the other hand, corresponded
well with the in vivo binding.
CONCLUSIONS. Monitoring the fraction of drug unbound in blood of an
individual rat throughout a pharmacokinetic experiment has now become possible
by using simultaneous sampling of blood and intravenous microdialysates.
AN: 96221672