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Traditionally the need for rapid attainment of a therapeutic blood concentration of a drug has meant that intravenous drug delivery has been the only method available for the treatment of status epilepticus or serial seizures. However, the technical problems associated with intravenous administration have prompted the evaluation of rectal dosage forms as a practical alternative.

Diazepam is rapidly absorbed from rectally delivered solution in propylene glycolwater-ethanol in healthy volunteers122. Suppository formulations of diazepam appear to be effective and safe in the prevention of recurrent febrile convulsions in children, suggesting that formulations with non-instantaneous release may be adequate for prophylactic therapy123. In adult epileptic patients, 10mg of diazepam in 2ml of an intravenous solution was administered rectally, and this resulted in serum concentrations comparable with those obtained after oral administration of a 10mg tablet; absolute rectal bioavailability amounted to 81%124. 'Valium' suppositories however have a bioavailability of just less than 70%, but have a very slow rate of absorption, with a Tmax ranging from 90 to 480 mins125.

Clonazepam, rectally administered as a suspension in 2.2 to 3.8ml of a propylene glycol-water mixture, also containing acetic acid, ethanol and benzylalcohol (Rivotril)

demonstrated rapid absorption. However, the intersubject variability was substantial. Sodium valproate is completely, although not rapidly, absorbed from an aqueous microenema (Tmax=2.2h) in healthy volunteers, whereas the absorption from a Witepsol H15 suppository was lower (Tmax=3.3h, bioavailability 89%). The rectal bioavailabilitv of sodium valproate appears to be better than that of enteric coated tablets which are erratically absorbed.

Rectal absorption of phenobarbital and its sodium salt from aqueous microenemas and suppositories is relatively slow126. The sodium salt, dissolved in a vehicle containing 10% alcohol and 75% propylene glycol, resulted in a rectal bioavailability of 90% relative to intramuscular administration. However, rectal absorption was delayed compared to intramuscular delivery (Tmax=4.4 h compared to 2.1 h). Consequently, this formulation could be considered as an alternative to intramuscular injection, but is not appropriate for the treatment of status epilepticus.

An aqueous suspension of carbamazepine, which also contained propylene glycol, sorbitol and sucrose, resulted in slow absorption of carbamazepine at a dose of 400 to 600mg, with a mean T of 6.3 h and C of 5.1 mg.L-1. This can probably be explained c max max o r J r by the poor water solubility of the compound. The bioavailability was 80% and 67% relative to oral tablets and oral suspensions respectively. Hence the rectal suspension was useful in maintaining administration in case of interrupted oral therapy. Unfortunately it was highlv irritant, indicating the need to optimise the formulation127. An aqueous suspension of 200 mg of carbamazepine containing 30% sorbitol showed a rectal bioavailability of 80% relative to the same suspension delivered orallv128. However, this formulation was difficult to retain, possibly because of a laxative effect of sorbitol.

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