logical action by stimulating receptors in the gastric mucosa. This increases the output from secretory glands of the gastrointestinal system and reflexly increases the flow of fluids from glands lining the respiratory tract. The result is an increase in volume and decrease in viscosity of bronchial secretions. Other actions may include stimulating vagal nerve endings in bronchial secretory glands and stimulating certain centres in the brain which in mm enhance respiratory fluid flow. Guaifenesin produces its expectorant action within 24 hours.
5.2 Pharmacokinetic properties
Absorption
Pseudoephedrine
Pseudoephedrine is well absorbed from the gut following oral administration. After the administration of one 60 mg pseudoephedrine tablet to healthy adult volunteers, the Cmax for pseudoephedrine was approximately 180 ng/ml with tmax occurring at approximately 1.5 - 2.0 hours.
Guaifenesin
Guaifenesin is well absorbed from the gastro-intestinal tract following oral administration, although limited information is available on its pharmacokinetics. After the administration of 600 mg guaifenesin to healthy adult volunteers, the Cmax was approximately 1.4 micrograms/ml, with tmax occurring approximately 15 minutes after drug administration.
Distribution
The apparent volume of distribution of pseudoephedrine (Vd/F) was approximately 2.8 l/kg. No information is available on the distribution of guaifenesin in humans.
Metabolism and elimination
Pseudoephedrine
The t½ was approximately 5.5 hours. Pseudoephedrine is partly metabolised in the liver by N-demethylation to norpseudoephedrine, an active metabolite. Pseudoephedrine and its metabolite are excreted in the urine; 55 % to 90 % of a dose is excreted unchanged. The apparent total body clearance of pseudoephedrine ( Cl/F ) was approximately 6 - 6.5 ml/min/kg. The rate of urinary elimination is accelerated when the urine is acidified. Conversely, as the urine pH increases, the rate of urinary elimination is slowed.
Guaifenesin
Guaifenesin appears to undergo both oxidation and demethylation. Following an oral dose of 600 mg guaifenesin to 3 healthy male volunteers, the t½ was approximately 1 hour and the drug was not detectable in the blood after approximately 8 hours.
Pharmacokinetics in Renal Impairment
Following the administration of a pseudoephedrine-containing product (8 mg acrivastine + 60 mg pseudoephedrine) to patients with varying degrees of renal impairment, the Cmax for pseudoephedrine increased approximately 1.5 fold in patients with moderate to severe renal impairment when compared to the Cmax in healthy volunteers. The tmax was not affected by renal impairment. The t½ increased 3 to 12 fold in patients with mild to severe renal impairment respectively, when compared to the t½ in healthy volunteers.
There have been no specific studies of this product, or guaifenesin in renally impaired patients.
Pharmacokinetics in Hepatic Impairment
There have been no specific studies of this product, guaifenesin or pseudoephedrine in hepatic impairment.
Pharmacokinetics in the Elderly
After the administration of a pseudoephedrine-containing product ( 8 mg acrivastine + 60 mg pseudoephedrine ) to elderly volunteers, the t½ for pseudoephedrine was 1.4 fold that seen in younger healthy volunteers. The apparent Cl/F was 0.8 fold that se
