Relative Bioavailability, Metabolism and Tolerability of Rectally Administered Oxcarbazepine Suspension

Methods: Two subjects received 300mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1: 1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time-point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (Cmax) and time to reach C_max (t_max) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C_max and AUCs were compared using Wilcoxon signed-rank tests.

Results: Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C_max and AUC values were significantly lower following rectal administration (p < 0.01). The total amount of monohydroxy derivative excreted in the urine following rectal administration was 10 ± 5% of the amount excreted following oral administration. Oral absorption was consistent with previous studies. The most common adverse effects were headache and fatigue with no discernible differences between routes.