Pharmacokinetics of Primidone Elimination by Uremic Patients

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.

[1]  C. R. Turner Primidone Intoxication and Massive Crystalluria , 1980, Clinical pediatrics.

[2]  Edward L. Stern Possible phenylethylmalondiamide (pema) intoxication , 1977, Annals of neurology.

[3]  R. Kauffman,et al.  Kinetics of primidone metabolism and excretion in children , 1977 .

[4]  I. Lagenstein,et al.  Intoxication with primidone: continuous monitoring of serum primidone and its metabolites during forced diuresis. , 1977, Neuropadiatrie.

[5]  M. D. Levine Letter: Confirmation of antentally detected fetal abnormality. , 1974, Lancet.

[6]  R. Mattson,et al.  Acute primidone intoxication. , 1974, Archives of neurology.

[7]  D. Wyler Letter: B-cell mitogen in hypergammaglobulinaemia in malaria and trypanosomiasis. , 1974, Lancet.

[8]  B. Wilder,et al.  Rapid, simultaneous GLC determination of phenobarbital, primidone, and diphenylhydantoin. , 1973, Journal of pharmaceutical sciences.

[9]  B. Gallagher,et al.  Metabolism and anticonvulsant properties of primidone in the rat. , 1973, The Journal of pharmacology and experimental therapeutics.

[10]  R. Mattson,et al.  Metabolic disposition of primidone and its metabolites in epileptic subjects after single and repeated administration , 1972, Neurology.

[11]  P. Jatlow,et al.  Chemical analysis of massive crystalluria following primidone overdose. , 1972, American journal of clinical pathology.

[12]  R. Mattson,et al.  Phenylethylmalonamide (PEMA). An important metabolite of primidone. , 1972, Archives of neurology.

[13]  C. Tassinari,et al.  A Clinical Study of Serum Primidone Levels , 1970, Epilepsia.

[14]  J. Briggs,et al.  Successful treatment of three cases of very severe barbiturate poisoning. , 1969, Lancet.

[15]  M. Kappy,et al.  Primidone intoxication in a child. , 1969, Archives of disease in childhood.

[16]  J. Fujimoto,et al.  Urinary excretion of primidone and its metabolites in rabbits. , 1968, The Journal of pharmacology and experimental therapeutics.

[17]  James Bogan,et al.  The relation between primidone and phenobarbitone blood levels , 1968, The Journal of pharmacy and pharmacology.

[18]  M. Dam,et al.  THE METABOLIC CONVERSION OF PRIMIDONE (MYSOLINE®) TO PHENOBARBITONE IN PATIENTS UNDER LONG‐TERM TREATMENT , 1967, Acta neurologica Scandinavica.

[19]  A. Et An unusual case of primidone intoxication. , 1966 .

[20]  E. Ajax An unusual case of primidone intoxication. , 1966, Diseases of the nervous system.

[21]  V GELLMAN,et al.  POISON CENTRE REPORT. PRIMIDONE (MYSOLINE) INTOXICATION. , 1965, Manitoba medical review.

[22]  R. Handley,et al.  Mysoline; a new drug in the treatment of epilepsy. , 1952, Lancet.