Pharmacokinetics of primidone elimination by uremic patients

The hemodialyzability of primidone was investigated in four patients on long-term hemodialysis. Primidone, 500 or 250 mg, was given orally 2 hours before hemodialysis. Blood and dialyzate samples were collected periodically during the 4-hour dialysis and measured by gas-liquid chromatography and high-performance liquid chromatography for primidone. Dialysis clearance calculated by the instantaneous dialyzate method averaged 97.7 ml/min, which is considerably greater than the metabolic clearance of 30 ml/min for the drug. The extraction efficiency of the hollow-fiber dialyzers averaged 40.2 pr cent for plasma samples. A mean of 31.7 per cent of the administered dose of primidone was removed during hemodialysis. The half-life was 5.1 hours in our patients during hemodialysis, a nearly two-thirds reduction of the 13.9-hour half-life calculated in uremic patients. Because of the reduction in elimination half-life, greater dialysis clearance than metabolic clearance, high extraction efficiency, and significant drug removal during dialysis, we conclude that primidone is dialyzable.