Source: Υπουργείο Υγείας (CY) Revision Year: 2020 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Pharmacotherapeutic group: Opium derivatives and expectorants
ATC code: R05FA02
Pseudoephedrine has a direct and indirect sympathomimetic activity and is an orally effective upper respiratory tract decongestant. Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation in systolic blood pressure and considerably less potent in causing stimulation of the central nervous system. Pseudoephedrine produces its decongestant effect within 30 minutes, persisting for at least 4 hours.
Triprolidine provides antihistamine activity by antagonising H1 receptors. Triprolidine provides symptomatic relief in conditions believed to depend wholly or partially upon the triggered release of histamine. It is a potent competitive histamine H1-receptor antagonist of the pyrrolidine class with mild central nervous system depressant properties which may cause drowsiness. After oral administration of a single dose of 2.5 mg triprolidine to adults, the onset of action as determined by the ability to antagonise histamine-induced weals and flares in the skin is within 1 to 2 hours. Peak effects occur at about 3 hours and, although activity declines thereafter, significant inhibition of histamine-induced weals and flares still occur 8 hours after the dose.
Dextromethorphan has an antitussive action. It controls coughs by spasms by depressing the medullary cough centre.
Guaiphenesin is thought to exert its pharmacological 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 turn enhance respiratory fluid flow. Guaiphenesin produces its expectorant action within 24 hours.
Pseudoephedrine is rapidly and completely absorbed after oral administration. After an oral dose of 180 mg to man, peak plasma concentrations of 500-900 ng/ml were obtained about 2 hours post dose. The plasma half life was approximately 5.5 hours and was increased in subjects with alkaline urine and decreased in subjects with acid urine. The apparent volume of distribution of pseudoephedrine (vd/f) was approximately 2.8 l/kg.
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 and unchanged. The apparent total body clearance of pseudoephedrine (c1/f) was approximately 7.5 ml/nim/kg. The elimination rate constant (kel) was approximately 0.13 hr-1. 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. Excretion was mainly via the urine.
In common with other antihistamines, triprolidine hydrochloride is rapidly absorbed, peak plasma levels being observed 2 hours after an oral dose, metabolised in the liver and excreted, mainly as metabolites in the urine. The plasma half life is approximately 3.2 hours. In pharmacokinetic studies, the apparent volume of distribution of triprolidine was approximately 6.5 l/kg for the tablet formulation and 7.5 l/kg for the syrup. Animal hepatic microsomal enzyme studies have revealed the presence of several triprolidine metabolites with an oxidised product of the toluene methyl group predominating. In man, it has been reported that only about 1% of an administered dose is eliminated as unchanged triprolidine over a 24-hour period. The apparent total body clearance of triprolidine (cl/f) was approximately 30-37 ml/min/kg. The elimination rate constant (kel) was approximately 0.26 hr-1.
Dextromethorphan undergoes rapid and extensive first-pass metabolism in the liver after oral administration. Genetically controlled O-demethylation (CYD2D6) is the main determinant of dextromethorphan pharmacokinetics in human volunteers.
It appears that there are distinct phenotypes for this oxidation process resulting in highly variable pharmacokinetics between subjects. Unmetabolised dextromethorphan, together with the three demethylated morphinan metabolites dextrorphan (also known as 3-hydroxy-N-methylmorphinan), 3-hydroxymorphinan and 3-methoxymorphinan have been identified as conjugated products in the urine.
Dextrorphan, which also has antitussive action, is the main metabolite. In some individuals metabolism proceeds more slowly and unchanged dextromethorphan predominates in the blood and urine.
Guaiphenesin is well absorbed from the gastro-intestinal tract following oral administration, although limited information is available on its pharmacokinetics. No information is available on the distribution of guaiphenesin in humans. Guaiphenesin appears to undergo both oxidation and demethylation. Following an oral dose of 600 mg guaiphenesin to 3 healthy male volunteers, the T½ was approximately 1 hour and the drug was not detectable in the blood after approximately 8 hours.
The active ingredients are well-known constituents of medicinal products and their safety profiles are well documented. The results of pre-clinical studies do not add anything of relevance for therapeutic purposes.
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