Relative bioavailability of topiramate administered rectally.
OBJECTIVE
To determine the relative bioavailability and tolerability of a topiramate (TPM) suspension after rectal administration.


METHODS
Seven healthy men and five healthy non-pregnant women were enrolled. A 100 or 200 mg tablet of TPM was given orally and a 200 mg 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 200 mg 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 200mg 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.
Conway
Jeannine M
JM
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. pluha003@umn.edu
Birnbaum
Angela K
AK
Kriel
Robert L
RL
Cloyd
James C
JC
D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D005632:Fructose / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077236:Topiramate
D000077236:Topiramate; D005632:Fructose