Pharmacokinetics of nomifensine in impaired renal function. 1977

S Ringoir, and N Lameire, and M Munche, and W Heptner, and K Taeuber

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.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D007676 Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION. ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D009627 Nomifensine An isoquinoline derivative that prevents dopamine reuptake into synaptosomes. The maleate was formerly used in the treatment of depression. It was withdrawn worldwide in 1986 due to the risk of acute hemolytic anemia with intravascular hemolysis resulting from its use. In some cases, renal failure also developed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p266) Hoe-984,Linamiphen,Merital,Nomifensin,Nomifensine Maleate,Nomifensine Maleate (1:1),Hoe 984,Hoe984,Maleate, Nomifensine
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D005919 Glomerular Filtration Rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance. Filtration Rate, Glomerular,Filtration Rates, Glomerular,Glomerular Filtration Rates,Rate, Glomerular Filtration,Rates, Glomerular Filtration
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006435 Renal Dialysis Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION. Dialysis, Extracorporeal,Dialysis, Renal,Extracorporeal Dialysis,Hemodialysis,Dialyses, Extracorporeal,Dialyses, Renal,Extracorporeal Dialyses,Hemodialyses,Renal Dialyses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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