Evaluation of acetaminophen P-glycoprotein-mediated salivary secretion by rat submandibular glands

PAULA SCHAIQUEVICH; VIVIANA NISELMAN; OMAR TUMILASCI; MODESTO RUBIO

ARCHIVES OF ORAL BIOLOGY

Elsevier

Año: 2004 vol. 49 p. 895 - 901

0003-9969

Summary The constant ratio between saliva and plasma acetaminophen concentra-tions (S/P) during the elimination phase is assumed to result from the equilibriumestablished among the free-drug concentrations in the arterial blood, venous blood andsaliva. Salivary secretion of acetaminophen is assumed to result from a passivediffusion of the drug to saliva from the blood that supplies the salivary glands.However, the constant S/P ratio during acetaminophen disposition and the findingthat P-glycoprotein (P-gp), a protein recognized to pump substrates out of the cell, isexpressed in duct cells of the submandibular glands questions themechanisms involvedin acetaminophen salivary secretion. Thus, we intended to evaluate the existence of aP-glycoprotein-mediated transport of acetaminophen in rat submandibular glands.Acetaminophen (30 mg/kg, i.v.) pharmacokinetics was assessed in controls and inrats pre-treated with erythromycin (100 mg/kg) as a P-glycoprotein inhibitor. Acet-aminophen pharmacokinetic parameters were calculated fromsaliva and plasma levelsconsidering a non-compartmental analysis.Mean plasma and salivary profiles of control and pre-treated animals were almostsuperimposable. No difference could be found in S/P ratios in control and erythromycinpre-treated animals (P > 0.05). Moreover, no statistical difference could be found inthe kinetic parameters calculated from saliva or plasma drug level (P > 0.05).These observations indicate that acetaminophen salivary secretion in rat subman-dibular glands is not related to P-glycoprotein-mediated transport under the experi-mental conditions of the present work.