Absorption of rectally administered phenytoin: a pilot study.
OBJECTIVE
To test the hypothesis that rectally administered phenytoin is absorbed in healthy volunteers.


METHODS
This single-center, open-label crossover pilot study compared rectal absorption with intravenous administration of phenytoin injectable solution (7 mg/kg) in healthy volunteers. Twelve serial blood samples were taken from each volunteer beginning at time zero until 36 hours following administration. These were analyzed for presence of phenytoin by immunoassay.


METHODS
The study took place at St. Paul's Hospital, a tertiary care center.


METHODS
Funding permitted for a sample size of five healthy participants, two men and three women, aged 21-45 years. Selection was by volunteer sample. Inclusion criteria were as follows: no known medical conditions, not receiving medication, no history of adverse drug reactions or allergies, not known to be pregnant, and normal liver function as determined per study protocol.


METHODS
Signs of absorption as indicated by presence of phenytoin in blood samples, maximum concentrations (Cmax), time to Cmax (tmax), AUC, and apparent bioavailability.


RESULTS
Maximum mean concentrations of 2.4+/-1.1 mg/L (mean +/- SD) following rectal administration and 11.2+/-1.6 mg/L following intravenous administration were achieved during the first one to two hours (tmax in both treatment arms). Mean apparent bioavailability of the rectally administered phenytoin was 24.4+/-13.4% (15.8-44.1%).


CONCLUSIONS
Results from this pilot study demonstrate that rectal absorption of phenytoin begins within 30 minutes following single-dose administration and was reported by four out of five volunteers to be the preferred route. Further studies are required before extrapolation can be made to the patient population.
Chang
S W
SW
Pharmacy Department, St. Paul's Hospital, University of British Columbia, Vancouver, Canada. schang1234@hotmail.com
da Silva
J H
JH
Kuhl
D R
DR
D000285:Administration, Rectal; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010865:Pilot Projects; D013488:Suppositories
D000927:Anticonvulsants; D013488:Suppositories; D010672:Phenytoin