Pharmacokinetics of Primidone Elimination by Uremic Patients

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Abstract
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 per 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.