Absorption of valproic acid suppositories in human volunteers
G. B. Holmes, W. E. Rosenfeld, N. M. Graves, R. P. Remmel, G. H. Carlson and R. D. Kriel
Department of Pharmacy Practice, College of Pharmacy, University of Minnesota, Minneapolis.
The absorption of valproic acid administered by rectal suppository was
studied in six male volunteers. Valproic acid was incorporated into a
synthetic lipid base in our pharmacy. Each subject received 500 mg of
valproic acid by rectal suppository and 500 mg of oral valproate sodium
syrup one week apart; 13 blood samples were drawn to determine serum
concentrations over 48 hours after administration of each formulation.
Significant differences were evident in the amount absorbed, maximum serum
concentration, and time to achieve maximum serum concentration between the
oral and rectal formulations. Mean absorption after rectal suppository was
80%. Maximum serum concentration was 43.4 mg/L after oral administration
and 29.2 mg/L after rectal suppository. The time to achieve maximum serum
concentration was 1.0 hour after oral syrup and 3.1 hours after rectal
suppository. Absorption of the rectal suppository was consistent and
complete within 3 hours. The use of valproate sodium in rectal suppository
form can be a more convenient and satisfactory method of administering
valproic acid when the oral route is impossible. Dosage increases may be
necessary, and serum concentrations should be monitored.
