Abstract
Plasma concentrations of diazepam (DZP) and N-desmethyl-diazepam (N-desmethyl-DZP) were followed after a single rectal administration of DZP (0.5 mg/kg) to ten infants aged 5 to 23 months with febrile convulsions. Two types of preparations were used for the study; suppositories to 5 patients and solutions to other 5 patients.
Rectal administration of solutions resulted in a rapid increase in plasma concentrations of DZP. The therapeutic plasma levels (above 150 ng/ml) were attained within 10 minutes in all infants. The average peak concentration of DZP and the average peak time were 498.2±172.7 ng/ml and 0.20±0.18 hour, respectively.
On the other hand, DZP suppositories did not give the therapeutic level until 10 minutes to 1 hour after administration. The average peak time was 1.45±0.76 hours, which was significantly longer than that after rectal DZP solutions (p<0.05). The average peak concentration was 355.3±146.1 ng/ml, which was lower than that obtained from rectal solutions, although there was no statistical significance. However, the therapeutic plasma DZP levels were maintained for a longer period.
N-desmethyl-DZP appeared in plasma around 1 hour after rectal administration of both DZP preparations. Plasma levels of N-desmethyl-DZP continued to increase up to 48 hours.
One infant had a recurrence of seizure at 6 hours after the rectal administration of DZP suppository when the plasma DZP level was 119.6 ng/ml, which was below the presumed therapeutic range. No serious side effects were observed except for transient sedation in any patients.
These results may suggest that a single rectal administration of DZP solution (0.5 mg/kg) is effective for the treatment of acute seizures and for the prevention of recurrent seizures during the vulnerable period after the episode. The same dose of DZP suppository is recommended to the patients at home for the prevention of recurrent febrile convulsions.
