Alternate routes of antiepileptic drug administration: A clinical study of rectally administered oxcarbazepine suspension

Objective. Rectal administration of some AEDs is a viable alternative when oral therapy is temporarily unavailable. A study was designed to characterize the bioavailability and tolerability of oxcarbazepine (OXC) suspension administered rectally. A survey was also carried out to ascertain the current clinical utilization of alternate routes for AED administration.;Methods. The clinical study utilized a randomized, crossover design in ten healthy volunteers. Two subjects received 300 mg doses of OXC and eight received 450 mg doses. Urine and plasma were collected for 72 hours post-dose. Adverse effects were assessed using a self-administered questionnaire.;Clinician members of the American Epilepsy Society were emailed invitations to participate in the online survey. Respondents identified the specific AEDs and alternate routes they had utilized in clinical practice, selected reservations about using these routes, and ranked their preference for six theoretically available routes in three clinical scenarios.;Results. The mean relative bioavailability of MHD following rectal administration was 8.3 +/- 5.8% based on plasma data and 10 +/- 5% based on the amount excreted in urine. The most common adverse effects were headache and fatigue with no difference in AEs between routes.;Seventy-five clinicians responded to the survey. 88% had suggested an alternate route of AED administration to a patient at least once: 100% suggested it for seizure emergencies, 48% for short-term therapy, and 9% for long term use. The most frequently reported alternative was rectal diazepam; a total of 37 different combinations of AEDs and alternate routes have been recommended. In each clinical scenario, the preferred theoretically available route was transdermal and the least preferred was rectal.;Conclusion. The exposure to MHD after rectal administration of OXC suspension is significantly less than after oral administration. Both urine and plasma data indicated that only 8--10% of the OXC dose is absorbed following rectal administration. Rectal administration of diluted OXC suspension is therefore not recommended.;Alternate routes of administration were utilized by most survey respondents. Rectal diazepam was the most often recommended alternative route AED but rectal was the least preferred route. Additional research and commercial products could improve current options for epilepsy patients.