Effectiveness of Daily Primidone for the Prevention of Febrile Convulsions: A Further Study
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The necessity and effectiveness of anticonvulsant therapy for the prevention of febrile convulsions are controversial matters. However, the continuous prophylactic anticonvulsant therapy has been recommended by many recent studies, especially in children who are at an increased risk for developing neurologic sequelae and epilepsy.<BR>Faerø et al. (1972) reported that consistent prevention of recurrences of febrile convulsions is provided by using phenobarbital (PB) only when the plasma levels are maintained above 16 μg/m<I>l</I>. It was also suggested that primidone (PRM) is effective for prophylaxis of a new attack (Wallace, 1975; Cavazzuti, 1975).<BR>The present study aimed to assess the effectiveness of daily PRM for the prevention of febrile convulsions in relation to plasma levels of both PRM and PB derived from PRM.<BR>A total of 50 children aged 1-6 years who had febrile convulsions more than twice was classified into two groups; 25 as "simple" febrile convulsions (group A), and another 25 as "epilepsy triggered by fever"(group B). All children in both groups were given PRM of 15-20 mg/kg daily in two divided doses and were followed for 9 to 21 months. The plasma concentrations of PRM and PB were determined 4 to 6 weeks after the initiation of therapy at first and thereafter every 6 months. All blood samples were drawn 2-4 hours after the morning dose.<BR>Plasma levels of both PRM and PB in individual patients varied considerably and the majority of the patients (18 at the first and 14 at the second) had plasma PB levels clearly below the effective level (less than 16 μg/m<I>l</I>).<BR>All of these 50 children had febrile episodes during the follow-up period. However, only 5 patients (4 in group A, and 1 in group B) had new convulsions. In the cases of recurrence, plasma PRM levels ranged from 6.2 to 17.4 μg/m<I>l</I>, while the PB levels were less than 10 μg/m<I>l</I>.<BR>This study shows that the continuous therapy with PRM of ordinary dosage is effective for the prevention of febrile convulsion recurrences. The prophylactic effect seemed to be achieved by PRM itself, and not PB derived from PRM. However, an effective plasma level of PRM could not be established.<BR>In the present series of PRM mono-therapy, the initial plasma level/dose ratios had a tendency to decrease in PRM and to increase in PB during subsequent 6 months; at the first determination, daily dosage, plasma PRM level, plasma PB level and plasma PB/PRM level ratio were 18.2 ± 2.0 mg/kg, 9.1 ± 3.1 μg/m<I>l</I>, 11.3 ± 4.3 μg/m<I>l</I> and 1.4 ± 0.6, while at the second, these were 17.0 ± 2.0 mg/kg, 7.6 ± 3.4 μg/m<I>l</I>, 11.6 ± 5.5 μg/m<I>l</I> and 1.8 ± 1.3, respectively. These changes may suggest that PRM induces its own metabolism (autoinduction).
- 一般社団法人 日本小児神経学会の論文
一般社団法人 日本小児神経学会 | 論文
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