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UREX (methenamine hippurate) is readily absorbed from the GI tract. Methenamine distributes widely into body fluids, but very little is hydrolyzed prior to excretion in the kidney and thus has minimal systemic toxic potential.

Within one-half hour after a single 1 g dose of UREX (methenamine hippurate) , anti-bacterial activity is demonstrable in the urine. Urine shows continuous antibacterial activity when UREX (methenamine hippurate) is administered at the recommended dosage schedule of 1 g twice daily. Over 90% of the methenamine moiety is excreted in the urine within twenty-four hours after administration of a single 1 g dose. Similarly, the hippurate moiety is rapidly absorbed and excreted, and it reaches the urine by both tubular secretion and glomerular filtration. This may be of importance in older patients or those with some degree of renal impairment.

Methenamine is placentally transferred to the fetus during pregnancy.

Microbiology. UREX (methenamine hippurate) exerts its activity because the methenamine component is hydrolyzed to formaldehyde in acid urine. Hippuric acid, the other component, acts to keep the urine acid. The minimal inhibitory concentrations are significantly lower in more acidic media; therefore, the efficacy of UREX (methenamine hippurate) can be increased by acidification of urine (see DOSAGE AND ADMINISTRATION).

Microorganisms do not develop resistance to formaldehyde; however urea-splitting microorganisms (e.g. Proteus species) tend to raise the pH of the urine thus inhibiting the release of formaldehyde. When the urine pH is 6 and the daily urine volume is 1000 - 1500 mL a 2 g dose of UREX (methenamine hippurate) daily will yield a urinary concentration of 18 to 60 ug/mL of formaldehyde, this being more than the minimal inhibitory concentration for most urinary pathogens.

Animal Pharmacology And Animal Toxicology

Up to 600 mg/kg of UREX (methenamine hippurate) in a single dose have been administered intravenously to dogs and to rats without toxic effects being observed. Chronic oral administration of 50 to 200 mg/kg/day to dogs and 800 to 6400 mg/kg/day to rats produced gastric and bladder irritation with some hemorrhagic sites and ulceration observed at autopsy. Amounts of UREX (methenamine hippurate) equivalent to twice the recommended human dose were administered to rats for twelve months and to monkeys for six months without producing any adverse effects.

Last reviewed on RxList: 3/28/2008
This monograph has been modified to include the generic and brand name in many instances.

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