Evaluation of acetaminophen P-glycoprotein-mediated salivary secretion by rat submandibular glands.
The constant ratio between saliva and plasma acetaminophen concentrations (S/P) during the elimination phase is assumed to result from the equilibrium established among the free-drug concentrations in the arterial blood, venous blood and saliva. Salivary secretion of acetaminophen is assumed to result from a passive diffusion of the drug to saliva from the blood that supplies the salivary glands. However, the constant S/P ratio during acetaminophen disposition and the finding that P-glycoprotein (P-gp), a protein recognized to pump substrates out of the cell, is expressed in duct cells of the submandibular glands questions the mechanisms involved in acetaminophen salivary secretion. Thus, we intended to evaluate the existence of a P-glycoprotein-mediated transport of acetaminophen in rat submandibular glands. Acetaminophen (30 mg/kg, i.v.) pharmacokinetics was assessed in controls and in rats pre-treated with erythromycin (100 mg/kg) as a P-glycoprotein inhibitor. Acetaminophen pharmacokinetic parameters were calculated from saliva and plasma levels considering a non-compartmental analysis. Mean plasma and salivary profiles of control and pre-treated animals were almost superimposable. No difference could be found in S/P ratios in control and erythromycin pre-treated animals (P > 0.05). Moreover, no statistical difference could be found in the kinetic parameters calculated from saliva or plasma drug level (P > 0.05). These observations indicate that acetaminophen salivary secretion in rat submandibular glands is not related to P-glycoprotein-mediated transport under the experimental conditions of the present work.
Schaiquevich
Paula
P
Instituto de Investigaciones Farmacológicas, ININFA-CONICET, Facultad de Farmacia y Bioquímica, Junín 956, 5 piso (1113), Ciudad de Buenos Aires, Argentina. paulas@ffyb.uba.ar
Viviana
Niselman
N
Omar
Tumilasci
T
Modesto
Rubio
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004917:Erythromycin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012463:Saliva / Q000378:metabolism*; D013363:Submandibular Gland / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D004917:Erythromycin