PROTEIN-BINDING OF SOTALOL ENANTIOMERS IN YOUNG AND ELDERLY HUMAN ANDRAT SERUM USING ULTRAFILTRATION

The protein binding of sotalol (STL) enantiomers was evaluated using a n ultrafiltration technique with serum from young (32 +/- 2 years, n = 5) and elderly (73 +/- 6 years, n = 5) male and female humans, and yo ung (8 weeks, n = 4) and elderly (60 weeks, n = 3) male Sprague-Dawley rats. Serum samples were collected and immediately frozen at -20 degr ees C. Within 1 week, the serum samples were thawed at room temperatur e, and adjusted to pH 7.4 using 0.05 M phosphate buffer, pH 5.0. Aliqu ots were spiked with 250 ng mL(-1) and 500 ng mL(-1) of each STL enant iomer, placed in ultrafiltration sets (Microsep, 30 K molecular weight cut-off), capped, equilibrated to 37 degrees C, and centrifuged at 18 50 g for 1.5 h at 37 degrees C. Aliquots of ultrafiltrate and unspun s erum were analysed for STL enantiomer concentration using a stereospec ific HPLC assay. In all groups, bound fraction was less than 7% for bo th STL enantiomers. There were no significant differences in bound fra ction between groups, or between enantiomers. Adsorption of STL enanti omers to the ultrafiltration device and membrane, evaporative loss of serum samples during centrifugation, and protein concentration in each ultrafiltrate sample were all negligible. It is concluded that the bi nding of STL in human and rat serum at therapeutic concentrations and physiological temperature and pH is negligible and nonstereoselective.