Dialysability of benzodiazepines by haemodialysis and controlled sequential ultrafiltration (CSU) in vitro

The efficacy of haemodialysis and controlled sequential ultrafiltration (CSU) for the elimination of three hypnotic and 6 benzodiazepine drugs was compared in vitro. In comparison to haemodialysis the efficacy of ultrafiltration by CSU was poor, as the mean per cent of CSU/haemodialysis (mg/hr) for 5 benzodiazepines was only 0.6-4.0% and for three hypnotics, phenobarbital 3.4%, pyrithyldione 8.2% and glutethimide 2.5% of the haemodialysis values. In haemodialysis in vitro phenobarbital, pyrithyldione, glutethimide and chlordiazepoxide were significantly and markedly more dialysable than 5 other benzodiazepines. The mean clearance of six benzodiazepine derivatives was about 2 to 3 times higher at blood flow rates of 200 ml/min. than 100 ml/min. In CSU experiments in vitro it was possible to remove approximately (as the mean percent of the initial dose) only the amount of five benzodiazepines corresponding to the per cent of the protein unbound fraction in the plasma (correlation r = 0.975, P less than 0.01). Only low amounts of three hypnotics, especially glutethimide, were removed by CSU in vitro.