Absorption of rectally administered phenytoin: A pilot study

OBJECTIVE: To test the hypothesis that rectally administered phenytoin is a bsorbed in healthy volunteers, DESIGN: This single-center, open-label crossover pilot study compared recta l absorption with intravenous administration of phenytoin injectable soluti on (7 mg/kg) in healthy volunteers. Twelve serial blood samples were taken from each volunteer beginning at time zero until 36 hours following adminis tration. These were analyzed for presence of phenytoin by immunoassay. SETTING: The study took place at St. Paul's Hospital, a tertiary care cente r. PARTICIPANTS: Funding permitted for a sample size of five healthy participa nts, two men and three women, aged 21-45 years. Selection was by volunteer sample. Inclusion criteria were as follows: no known medical conditions, no t receiving medication, no history of adverse drug reactions or allergies, not known to be pregnant, and normal liver function as determined per study protocol. MAIN OUTCOME MEASURES: Signs of absorption as indicated by presence of phen ytoin in blood samples, maximum concentrations (C-max). time to C-max (t(ma x)), AUC, and apparent bioavailability, RESULTS: Maximum mean concentrations of 2.4 +/- 1.1 mg/L (mean +/- SD) foll owing rectal administration and 11.2 +/- 1.6 mg/L following intravenous adm inistration were achieved during the first one to two hours (t(max) in both treatment arms). Mean apparent bioavailability of the rectally administere d phenytoin was 24.4 +/- 13.4% CONCLUSIONS: Results from this pilot study demonstrate that rectal absorpti on of phenytoin begins within 30 minutes following single dose administrati on and was reported by four out of five volunteers to by the preferred rout e. Further studies are required before extrapolation can be made to the pat ient population.