People aged 70–81, relative to people aged 18–26, have decreased renal clearance of primidone, phenobarbital, and PEMA, in ascending order of significance, and that there was a greater proportion of PEMA in the urine. The clinical significance is unknown. The percentage of primidone converted to phenobarbital has been estimated to be 5% in dogs and 15% in humans. Work done twelve years later found that the serum phenobarbital 0.111 mg/100 mL for every mg/kg of primidone ingested. Authors publishing a year earlier estimated that 24.5% of primidone was metabolized to phenobarbital. However, the patient reported by Kappy and Buckley would have had a serum level of 44.4 mg/100 mL instead of 8.5 mg/100 mL if this were true for individuals who have ingested large dose. The patient reported by Morley and Wynne would have had serum barbiturate levels of 50 mg/100 mL, which would have been fatal. History
Primidone is a congener of phenobarbital where the carbonyl oxygen of the urea moiety is replaced by two hydrogen atoms. The effectiveness of Primidone for epilepsy was first demonstrated in 1949 by Yule Bogue. He found it to have a similar anticonvulsant effect to phenobarbitol, but more specific, i.e. with fewer associated sedative effects.It was brought to market a year later by the Imperial Chemical Industry (ICI), now known as AstraZeneca in the United Kingdom and Germany. In 1952, it was approved in the Netherlands.Also in 1952, Drs.
Adverse effects
Primidone can cause drowsiness, listlessness, ataxia, visual disturbances, nystagmus, headache, and dizziness. These side effects are the most common, occurring in more than 1% of users. Transient nausea and vomiting are also common side effects. Dupuytrens contracture, a disease of the fasciae in the palm and fingers that permanently bends the fingers (usually the little and ring fingers) toward the palm, was first noted to be highly prevalent in epileptic people in 1941 by a Dr. Lund, fourteen years before primidone was on the market. Lund also noted that it was equally prevalent in individuals with idiopathic and symptomatic epilepsy and that the severity of the epilepsy did not matter. However, only one quarter of the women were affected vs. half of the men. Thirty-five years later, Critcheley et al. reported a correlation between how long a patient had had epilepsy and his or her chance of getting Dupuytrens contracture. They suspected that this was due to phenobarbital therapy, and that the phenobarbital was stimulating peripheral tissue growth factors. Dupuytrens contracture is almost exclusively found in Caucasians, especially those of Viking descent, and highest rates are reported in Northern Scotland, Norway, Iceland, and Australia. It has also been associated with alcoholism, heavy smoking, diabetes mellitus, physical trauma (either penetrating in nature or due to manual labor), tuberculosis, and HIV. People with rheumatoid arthritis are less likely to get this, and Drs. Hart and Hooper speculate that this is also true of gout due to the use of allopurinol.