title: Salivary flow induction by buccal permucosal pilocarpine in anesthetized beagle dogs.
abstract: 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.
authors.affiliation: University of Connecticut, School of Pharmacy, Storrs 06269.
authors.forename: M L
authors.initials: ML
authors.lastname: Weaver
authors.forename: J M
authors.initials: JM
authors.lastname: Tanzer
authors.forename: P A
authors.initials: PA
authors.lastname: Kramer
mesh_terms: D000278:Administration, Buccal; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D005260:Female; D006863:Hydrogen-Ion Concentration; D010862:Pilocarpine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D012463:Saliva / Q000378:metabolism; D012472:Salivation / Q000187:drug effects*; D012636:Secretory Rate; D014987:Xerostomia / Q000188:drug therapy
chemical_list: D010862:Pilocarpine