Journal of Dental Research, Vol 71, 1762-1767, Copyright © 1992 by International & American Associations for Dental Research Online Journals
Salivary flow induction by buccal permucosal pilocarpine in anesthetized beagle dogs
M. L. Weaver, J. M. Tanzer and P. A. Kramer
University of Connecticut, School of Pharmacy, Storrs 06269.
We tested whether permucosal delivery of pilocarpine nitrate could be used
to elicit significant salivary secretion. Pilocarpine (pKa 6.6 at 37
degrees C) was applied as solutions (pHs 5.6, 6.6, 7.6; 15 mg/mL) to the
buccal mucosa (2.8 cm2) of 6 anesthetized dogs. Saliva was collected
continuously from cannulated submandibular and parotid ducts and blood
sampled during and after drug administration. Plasma pilocarpine levels
were determined by reversed-phase HPLC. Absorption rates were determined by
use of data from separate zero-order intravenous infusions to the same
dogs. Pilocarpine was buccally absorbed at a constant rate of 72.9 +/- 38.5
micrograms/kg/h following its application at pH 7.6. At this pH of the drug
solution, the time to appearance of pilocarpine in blood plasma was 0.31
+/- 0.08 h, and the time to appearance of salivary flow was 0.86 +/- 0.32
h. A threshold dose of 32.9 +/- 7.5 micrograms/kg was required to induce
secretion with the pH 7.6 drug, the steady-state submandibular flow rate
was 0.14 +/- 0.11 mL/min/gland pair. Salivary flow induction was
symmetrical and reached levels as high as 0.35 mL/min/submandibular gland
pair without apparent tachyphylaxis. Results at pHs 5.6, 6.6, and 7.6 were
consistent with the hypothesis that pilocarpine is primarily absorbed as
un-ionized drug. The data indicate that transmucosal delivery of
pilocarpine, avoiding "first pass" hepatic loss, may hold promise for the
treatment of xerostomia.
