Epilepsy Research 54 (2003) 91–96 Relative bioavailability of topiramate administered rectally Jeannine M. Conway a,* , Angela K. Birnbaum a , Robert L Kriel a,b , James C. Cloyd a a Experimental and Clinical Pharmacology, Epilepsy Research and Education Program, College of Pharmacy, University of Minnesota, 7-170 WDH 308 Harvard St. SE, Minneapolis, MN 55455, USA b Departments of Pediatrics and Neurology, Hennepin County Medical Center, Minneapolis, MN, USA Received 18 October 2002; received in revised form 12 March 2003; accepted 18 March 2003 Abstract Objective: To determine the relative bioavailability and tolerability of a topiramate (TPM) suspension after rectal administra- tion. Design/method: Seven healthy men and five healthy non-pregnant women were enrolled. A 100 or 200 mg tablet of TPM was given orally and a 200mg dose was given rectally in a randomized, open-label, crossover study with at least a 2-week washout period between doses. Plasma samples were collected prior to dosing and the following times after each dose: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, and 96 h. Relative bioavailability was determined by calculating the ratio of the dose-normalized area under the curve (AUC/D) for the rectal and oral doses. Results: Ten subjects completed the study. Two of the first seven subjects who received a 200mg initial oral dose, withdrew because of side effects. The remaining subjects received a 100 mg oral dose. Three subjects received a 200 mg dose orally and rectally, and seven subjects received 100 mg orally and 200 mg rectally. The average AUC/D was 0.72 ±0.18 h/l for the rectal dose and 0.76 ± 0.20 h/l for the oral dose. The relative bioavailability (n = 10) for TPM administered rectally was 0.95 ± 0.17 with a range of 0.68–1.2. There were no statistically significant differences between the oral or rectal pharmacokinetic parameters. Conclusions: In healthy adults, rectally administered TPM is absorbed to a similar extent as the oral dosage form. Rectal administration is an acceptable route of administration for TPM, when the oral route is temporarily unavailable. © 2003 Elsevier Science B.V. All rights reserved. Keywords: Topiramate; Rectal administration; Bioavailability 1. Introduction A common cause of seizure breakthrough is interruption in antiepileptic drug (AED) therapy (Krumholz et al., 1989). Missing doses may have catastrophic effects on a patient’s seizure control, in- cluding increased frequency, intensity, or duration of * Corresponding author. Tel.: +1-612-625-2999; fax: +1-612-626-0148. E-mail address: pluha003@umn.edu (J.M. Conway). seizures (Stanaway et al., 1985). Although noncom- pliance is the most common reason for interruptions of oral therapy, there are a variety of other reasons such as vomiting, gastrointestinal illness, fasting prior to and after surgery, and impairment of conscious- ness that may result in a precipitous decrease in AED blood concentrations. Alternatives to oral AED therapy are limited. Among all the AEDs only three are available as parenteral formulations: phenobarbital, phenytoin, and sodium valproate. This leaves many patients 0920-1211/03/$ – see front matter © 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0920-1211(03)00083-4