Abstracts

RATIONALE: The inability to use the oral route of administration poses a significant clinical problem for antiepileptic drugs (AEDs) because many AEDs are not available in a parenteral formulation. The rectal route may be an acceptable alternative to the oral route of administration if the drug is absorbed consistently and is well tolerated. The objective of this study was to determine the relative bioavailability of a topiramate (TPM) suspension after rectal administration.
METHODS: Twelve healthy men (n=7) and non-pregnant women (n=5) were enrolled in the study approved by both the University of Minnesota and Hennepin County Medical Center[ssquote]s human subjects committees. A 100-mg or 200-mg tablet 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. For rectal administration, tablets were crushed and suspended in 20 mls of water. Subjects were admitted to the Hennepin County clinical research unit for drug administration through the 24-hour specimen collection. Plasma samples were collected at the following times after each dose: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 hours. The plasma samples were analyzed for TPM by GC-MS. Relative bioavailability was determined by calculating the ratio of the dose normalized area under the curve (AUC/D) for the rectal dose to the AUC/D for the oral dose.
RESULTS: Ten subjects completed the study. Two subjects withdrew because of side effects following the initial 200-mg oral dose. Therefore, the remaining subjects received a 100mg oral dose. Three subjects received 200-mg orally and rectally and seven subjects received 100-mg orally and 200-mg rectally. The time to peak plasma concentrations was longer for the rectal dose averaging 2.6 hrs (S.D. 0.5 hrs) versus the oral dose averaging 1.8 hrs (S.D. 1.5 hrs). The average dose adjusted area under the curve (AUC/D) for the rectal dose was 0.76 hr/L (S.D. 0.19) and 0.79 hr/L (S.D. 0.22) for the oral dose. The relative bioavailability (n=10) for TPM administered rectally was 0.97 (S.D. 0.18, range 0.68-1.2).
CONCLUSIONS: In healthy adults, TPM is absorbed rectally to a similar extent as compared to the oral dosage form. This information will help guide the practitioner and care givers about an alternate route of administration when oral delivery is not possible.
Support: USP Fellowship
R.W.Johnson Pharmaceutical Research Institute
Disclosure: Grant - R.W. Johnson Pharmaceutical Research Institute