Methenamine hippurate is a broad-spectrum urinary antiseptic agent. Under acidic conditions, methenamine hippurate is hydrolyzed to formaldehyde and ammonia, which exerts an antibacterial effect. It is effective against a wide range of bacteria but lacks activity against Proteus and other bacteria that increase urine alkalinity. Formulations containing methenamine hippurate have been used to treat urinary tract infections.
Hiprex ,Merrell National,US,1967
ChEBI: Methenamine hippurate is a N-acylglycine. It is functionally related to a N-benzoylglycine.
179 g (1 mol) hippuric acid (benzoyl glycine) and 140 g (1 mol) hexamethylenetetramine were heated under reflux in 500 ml methanol. The small amount of water necessary to give a clear, homogeneous solution was added to the resulting reaction mixture which was then evaporated to
dryness. The residue soon crystallized, a procedure that could be greatly
accelerated by seeding with crystals of hexamethylenetetramine hippurate
from a previous preparation. The resulting solid product was broken up and
pulverized. Hexamethylenetetramine hippurate is stable on exposure to air
and is soluble in water and alcohol. It melts at 105° to 110°C.
Methenamine hippurate (Hiprex) is the hippuric acid salt ofmethenamine. It is readily absorbed after oral administrationand is concentrated in the urinary bladder, where it exerts itsantibacterial activity. Its activity is increased in acid urine.
Potentially hazardous interactions with other drugs
Antibacterials: increased risk of crystalluria with
sulphonamides.
Diuretics: effects antagonised by acetazolamide.
Under acid conditions methenamine is slowly hydrolysed
to formaldehyde and ammonia. Almost no hydrolysis of
methenamine takes place at physiological pH, and it is
therefore virtually inactive in the body. Methenamine is
rapidly and almost completely eliminated in the urine,
and provided this is acidic (preferably below pH 5.5)
bactericidal concentrations of formaldehyde occur.
Because of the time taken for hydrolysis, however, these
do not occur until the urine reaches the bladder.
[1] GRAYSON M, WHITBY M. Methenamine Mandelate and Methenamine Hippurate[C]. 2010: 0. DOI:
10.1201/b13787-101
