Microdialysis: An Alternative for in Vitro and in Vivo Protein Binding Studies |
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Authors: | Quellec Anne Le Dupin Sylvie Tufenkji Ala Eldin Genissel Patrick Houin Georges |
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Affiliation: | (1) Laboratoire de Pharmacologie-Pharmacocinétique, Faculté des Sciences Pharmaceutiques et Unité de Pharmacocinétique Clinique, CHU Purpan, Place Baylac, 31059 Toulouse Cedex, Toulouse, France;(2) Technologic Servier, Orléans, France |
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Abstract: | The aim of the present study was to compare the performance of conventional equilibrium dialysis method with a microdialysis method in studying drug protein binding. The two methods were assessed by comparing the 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 membrane 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 gave 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 conditions, 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. |
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Keywords: | microdialysis protein binding equilibrium dialysis in vitro-in vivo binding |
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