Mechanism of action
Like other antihistamines, doxylamine acts by competitively inhibiting histamine at H1 receptors. It also has substantial sedative and anticholinergic effects.
Pharmacodynamics
Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power far superior to virtually every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most powerful over-the-counter sedative available in the United States, and more sedating than many prescription hypnotics. In a study, it was found to be superior to even the barbiturate, phenobarbital for use as a sedative. Doxylamine is also a potent anticholinergic.
Pharmacokinetics
Half-life
10 hours
The drug has an elimination half-life of about 10 hours in healthy adults.
Absorption
Readily absorbed via the gastrointestinal tract.
H1 antagonists are eliminated more rapidly by children than by adults and more slowly in those with severe liver disease. /H1 Receptor Antagonists/
The H1 antagonists are well absorbed from the gastrointestinal tract. Following oral administration, peak plasma concentrations are achieved in 2 to 3 hours ... . /H1 Receptor Antagonists/
Elimination and metabolic profiles of the glucuronide products of doxylamine and its N-demethylated metabolites were determined after the oral admin of (14)C-doxylamine succinate (13.3 and 133 mg/kg doses) to male and female Fischer 344 rats. The cumulative urinary and fecal eliminations of these conjugated doxylamine metaboites at the 13.3 mg/kg dose were 44.4 + or - 4.2% and 47.3 + or - 8.1% of the total recoverd dose for male and female rats, respectively. The cumulative urinary and fecal eliminations of conjugated doxylamine metabolites at the 133 mg/kg dose were 55.2 + or - 2.6% and 47.9 + or - 2.5% of the total recovered dose for male and female rats, respectively. The conjugated doxylamine metabolites that were isolated, quantitiated, and identified are doxylamine O-glucuronide, N-desmethyl-doxylamine O-glucuronide, and N,N-didesmethyldoxylamine O-glucuronide.
The elimination of doxylamine and metabolites was determined after iv admin of (14)C-doxylamine succinate at 0.7 and 13.3 mg/kg to the adult female rhesus monkey. Although the total recovery of radioactivity was the same for the low- and high-dose studies (90.2%), the rate of plasma elimination of doxylamine and its demethylated metabolite (desmethyldoxylamine) was slower for the high dose group. The 24 hr urinary excretion of doxylamine metabolites, desmethyl- and didesmethyldoxylamine, was significantly incr and the polar doxylamine metabolites were significantly decr as the iv doxylamine succinate dose was incr. The plasma elimination of GC-detected doxylamine was determined after po admin of Bendectin (doxylamine succinate and pyridoxine hydrochloride) /also contains dicyclomine hydrochloride/ at 7, 13.3, and 27 mg/kg to adult female rhesus monkeys. As the dose incr, the clearance of doxylamine decr. A statistically evaluated fit of the po data to a single-compartment, parallel first-order elimination model and a single-compartment, parallel first- and second-order (Michaelis-Menten) elimination model indicated that the more complex model containing the second-order process was most consistent with the observed elimination data. /Doxylamine succinate/
Metabolism
Hepatic.
The conjugated doxylamine metabolites that were isolated, quantitiated, and identified are doxylamine O-glucuronide, N-desmethyl-doxylamine O-glucuronide, and N,N-didesmethyldoxylamine O-glucuronide.
Analysis of doxylamine N-oxide and pyrilamine N-oxide as synthetic standards and biologically derived metabolites by thermospray mass spectrometry (TSP/MS) provided (M + H) + ions for each metabolite. ... In addition, TSP/MS and TSP/MS/MS analysis of ring-hydroxylated N-desmethyldoxylamine ... is also reported.
Hepatic.
Half Life: 10 hours
External links
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