Pharmacokinetics of levetiracetam after rectal administration in healthy volunteers

Objective: To investigate whether rectal administration is an alternative for oral administration by comparing the pharmacokinetics of levetiracetam after single-dose rectal versus oral administration in healthy volunteers. Design: Single-centre, open-label, single-dose, crossover study. Methods: We included 13 healthy volunteers who received a levetiracetam 500 mg tablet and after a washout period of at least 7 days, a levetiracetam 500 mg suppository. Blood samples were collected before administration and several times within the first 24 hours after administration of the tablet or suppository, to quantify levetiracetam plasma concentrations. WinNonlin was used to analyse the data. Results: A one-compartment model was suitable for both oral and rectal administration. The AUC of oral and rectal administration was 6406 vs 6690 mg·l-1·min (p = 0.557). The mean relative bioavailability (AUCrectal/AUCoral) was 104% (SD 23). It took more time to reach maximum peak concentration for the suppository (t max 190 vs 78 min), resulting also in a lower maximum concentration for the rectal administration (Cmax 7.56 vs 11.65 mg/ml). Conclusion: Rectal administration is an alternative for oral administration, since there was no significant difference in bioavailability (AUC). Follow-up research should include multi-dose administration and patients with epilepsy.
Pharmacokinetics of levetiracetam after rectal administration in healthy volunteers | Request PDF. Available from: https://www.researchgate.net/publication/289201747_Pharmacokinetics_of_levetiracetam_after_rectal_administration_in_healthy_volunteers [accessed Jan 16 2018].

De rectale toediening schijnt dus een alternatief voor de orale weg. U moet vertrekken van filmomhulde tabletten die u moet fijnmaken tot poeder. De beste methode , die ook anderen reeds gebruikten in dergelijke gevallen, is malen met een electrische koffiemolen. Het verkregen poeder wordt gezeefd en wat op de zeef achter blijft zijn hoofdzakelijk brokjes van de filmlaag. Men kan de zeefrest proberen een tweede keer te malen en te zeven. Zijn de filmrestjes niet fijn te krijgen dan worden ze verwijderd.