Pharmacokinetics of nomifensine in impaired renal function

1. In uremia, an increased frequency of adverse drug reactions is observed at elevated plasma levels of active drug. This is a consequence of decreased renal elimination of unchanged drug or pharmacologically active metabolites. 2. To study the pharmacokinetics of nomifensine in uremia, a single dose of nomifensine maleate 50 mg was given to 10 patients with a glomerular filtration rate between 0 and 61 ml/min. In three additional patients on maintenance haemodialysis, the influence of dialysis on the elimination of nomifensine after single oral doses of 50 mg was studied. 3. Blood samples were obtained before and at regular half-hourly or hourly intervals after administration. Plasma levels of nomifensine were examined using a radioimmunological determination method and pharmacokinetic parameters were calculated by computer program. 4. Whereas in healthy subjects the half-life of nomifensine was found to be 1.8 h, this parameter was found to be prolonged in renal patients. In a patient with a creatinine clearance of 0 ml/min the elimination half-life was 46 hours. Nomifensine is not eliminated by haemodialysis. 5. Our findings suggest that nomifensine should not be administered to renal patients with a glomerular filtration rate below 25 ml/minute.