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Rectal absorption and disposition of secobarbital in epileptic children
Insights
Rectal secobarbital solution offers faster absorption and higher peak concentrations than suppositories in epileptic children. Rectal solutions may provide a more rapid onset for prolonged seizure treatment.
Area of Science:
- Pharmacology
- Pediatric Epilepsy
Background:
- Rectal administration of anticonvulsants is used for seizure emergencies.
- Secobarbital is a barbiturate with sedative and anticonvulsant properties.
Purpose of the Study:
- To compare the absorption and disposition of rectally administered secobarbital in solution versus suppository form in epileptic children.
- To evaluate the safety and efficacy of different rectal secobarbital formulations for potential use in prolonged seizures.
Main Methods:
- Ten epileptic children (ages 2-13) received a single rectal dose of secobarbital (approx. 5 mg/kg).
- Five received secobarbital in solution, and five received suppositories.
- Serum secobarbital concentrations were measured over 48 hours.
Main Results:
- Absorption was significantly faster with rectal solution (0.92 hr) compared to suppositories (4.60 hr).
- Peak serum concentrations were higher with the solution (2.26 µg/ml) versus suppositories (1.35 µg/ml), remaining below toxic levels.
- Elimination half-life varied widely (2.7-13.5 hr) but did not differ between formulations. Extent of absorption was similar.
Conclusions:
- Rectal secobarbital solution provides a more rapid and consistent onset of action than suppositories.
- Rectal secobarbital solution may be a preferable option for the acute treatment of prolonged seizures in children.
- Further studies are warranted to confirm efficacy and optimal dosing.
Abstract:
The absorption and disposition of rectally administered secobarbital was studied in ten epileptic children, ages 2-13 yrs. Five subjects received secobarbital rectally in solution, and the other five received secobarbital suppositories. Concentration of secobarbital in serum was serially determined during 48 hrs after a single rectal dose of about 5 mg/kg. The rate of absorption of secobarbital, as measured by the time to reach peak serum concentration, was much more rapid from the solution than the suppository (0.92 +/- 0.47 hr vs 4.60 +/ 2.30 hr). The peak serum concentration of secobarbital in the solution group was consistently higher than in the suppository group (2.26 +/- 0.37 micrograms/ml vs 1.35 +/- 0.24 microgram/ml). None of the individual peak serum concentrations exceeded 3 micrograms/ml, which is well below the previously reported minimum toxic concentration of secobarbital (ie, 6 microgram/ml). The elimination half-life of secobarbital varied over a wide range, from 2.7 to 13.5 hr, and is, on the average, shorter than estimates previously reported for adult volunteers or poly-drug abusers. Also, the mean elimination half-life did not differ between the solution and the suppository groups. The extent of rectal absorption of secobarbital, as assessed by the area under the serum concentration time curve, was not significantly different between the solution and the suppository treatments. If rectal secobarbital is considered for treatment of prolonged seizure, a rectal solution may offer a more rapid and consistent onset of action than with the suppository preparation.