MICRODIALYSIS - AN ALTERNATIVE FOR IN-VITRO AND IN-VIVO PROTEIN-BINDING STUDIES

The aim of the present study was to compare the performance of convent ional equilibrium dialysis method with a microdialysis method in study ing drug-protein binding. The two methods were assessed by comparing t he measured mean unbound drug fraction in different plasma species in vitro in plasma of four different species and at two concentrations of the non-indolic melatonin analog S 20098. For the microdialysis study , the unbound drug fraction was calculated after correction for membra ne recovery. Plasma protein binding of S 20098 ranged from 75 to 95%. In humans, rabbits and rats (10 ng/ml), equal unbound percentages were found between equilibrium dialysis and microdialysis. Microdialysis g ave slightly but significantly higher values in rat (2000 ng/ml), and in monkey plasma independent of the drug concentration. Microdialysis was also performed in vivo in freely moving rats under steady-state co nditions, yielding similar unbound fraction values (26.0 +/- 0.9%) to those obtained using microdialysis probes in rat plasma in vitro (24.4 +/- 1.6%). These results support the use of in vivo microdialysis in pharmacokinetic studies in freely moving animals.