Effect of mode of administration on guaifenesin pharmacokinetics and expectorant action in the rat model

Aim: Guaifenesin is a very commonly used and prescribed oral expectorant drug. However, its mechanism of action is not completely elucidated and the available information is limited. The purpose was to evaluate whether guaifenesin action on respiratory tract secretion is mediated through a reflex stimulation of the gastric mucosa or by the systemic exposure due to the absorption of the drug to the blood circulation.

Methods: Guaifenesin was administered to rats by various routes: intravenous bolus, oral gavage, and gastric, jejunal or cecal infusions (through surgically implanted catheters). Phenol red respiratory tract secretion (after intraperitoneal or intravenous injection) was used as a marker for degree of expectorant action. Administration of saline by gavage was used as control.

Results: Respiratory secretion following oral bolus was approximately 2-fold higher (p<0.05) than that of control. Following IV administration the increase of respiratory secretion did not occur despite the fact that systemic exposure to guaifenesin was 1.5-fold higher than following oral administration. The abdominal surgery was found to eliminate the effect of guaifenesin although it did not change systemic absorption. Guaifenesin was equally absorbed from all parts of the gastrointestinal tract.

Conclusions: It was demonstrated that expectorant action of guaifenesin is mediated by stimulation of the gastrointestinal tract and not by the systemic exposure to the drug.