Comparative evaluation of microultrafiltration devices for determination of protein binding

The free fraction of drugs was determined comparatively with new microultrafiltration devices, Molcut II (Catalogue No. SJGC type) (MLII) and (Catalogue No. PLGC type) (NML; a device derived by changing the membrane component of MLII), which were developed by Nihon Millipore Ltd., Tokyo, Japan. The results obtained with the device are compared with those of MPS-1 (MPS), which is commercially available from Amicon Co., Danvers, MA, U.S.A. Drugs tested are phenytoin, carbamazepine, valproic acid, theophylline, phenobarbital, and gliclazide. In five of six drugs the free fraction by MLII shows lower values, although that by NML is in good agreement with MPS. The lower values of free fraction of drugs obtained with MLII may be caused by adsorption to the device. The adsorption increase is relatively correlated to increasing lipophilicity of drugs. The results suggest that physicochemical properties of each drug, especially hydrophobicity, should be taken into account, when a new device is used to examine protein binding of drugs. The NML, which is less expensive and is convenient because no special instrument is needed, is a reliable and satisfactory device for routine therapeutic free drug monitoring.