[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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[in Japanese]

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Recent studies in Europe have indicated that intermittent therapy with rectal administration of diazepam (DZP) suppository is effective in preventing recurrent febrile convulsions. However, DZP suppository has not been marketed in Japan.
The present study was designed to assess pharmacokinetically whether intermittent administration of oral DZP has comparable therapeutic efficacy with that of rectal DZP in the prevention of recurrent febrile convulsions.
Plasma concentrations of DZP and N-desmethyl-DZP were followed closely for the first 48 hours after a single oral administration of 0.5 mg/kg of DZP syrup in 6 infants aged 5 to 24 months with febrile convulsions. Pharmacokinetic parameters of DZP were calculated using the equation for a two compartment open model. The data were compared with those obtained after rectal administration of DZP suppository in another group of patients reported previously.
Therapeutic plasma levels of DZP (above 150ng/ml) were attained within 5 minutes and were maintained for about 8 hours after oral administration. Plasma concentrations of DZP 3 and 5 minutes after oral administration of DZP syrup were significantly higher than those after rectal administration of DZP suppository.
However, there were no significant differences in any of the pharmacokinetic parameters between the two groups. The parameters (Mean±SD) of DZP after a single oral dose of DZP were as follows; Cm. 590.4±196.3 ng/ml, tmax 1.00±0.69 hr, Ka 2.762±2.521 hr^-1, t1/2β 31.1±2.9 hr, [ACU] ^∞₀ 8703.0±1409.0ng/ml·hr, Cl/F 0.058±0.008l/hr/kg, Vd_area/F 2.61±0.49l/kg.
Plasma concentrations of N-desmethyl-DZP, which has also been considered to have an anticonvulsant effect, continued to increase slowly up to 24 hours after oral administration of DZP syrup in a lower range compared with DZP levels.
These results may suggest that intermittent prophylactic administration of oral DZP syrup has comparable therapeutic effect with that of rectal DZP suppository in preventing recurrent febrile convulsions.

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