A mixture of 0.1 mol of N-mono-1-p-chlorobenzohydrylpiperazine and 0.1 mol
of 1-chloro-2-(2-hydroxy-ethoxy)-ethane is heated for 3 hours to 150°C. The
mass is then taken up in 100 ml of benzene and 100 ml of a 10% aqueous
solution of NaOH; decanting takes place, and the benzene solution is washed
with water and the solvent is evaporated. Vacuum distilling of the residue
yields 1-p-chlorobenzohydryl-4-[2-(2-hydroxy-ethoxy)-ethyl]-piperazine, BP
220°C/0.5 mm Hg.
The corresponding dihydrochloride is prepared by dissolving this base in about
twice its weight of alcohol, by treating it with excess of gaseous HCl and by
precipitating it with ether. The solvent is decanted and the residue, dissolved
in a minimum of alcohol, crystallizes on the addition of ether, MP 193°C.
Antihistamine:
Pruritus
Anxiety (short-term)
Potentially hazardous interactions with other drugs
Analgesics: sedative effects possibly increased with
opioid analgesics.
Hydroxyzine is extensively metabolised. The formation
of the major metabolite cetirizine, a carboxylic acid
metabolite (approximately 45% of the oral dose), is
mediated by alcohol dehydrogenase. This metabolite has
significant peripheral H1-antagonist properties. The
other metabolites identified include a N-dealkylated
metabolite, and an O-dealkylated metabolite with a
plasma half-life of 59 hours. These pathways are mediated
principally by CYP3A4/5. Only 0.8% of the dose is
excreted unchanged in urine. The major metabolite
cetirizine is excreted mainly unchanged in urine (25% and
16 % of the hydroxyzine oral and IM dose, respectively).
