Methenamine

Methenamine is a urinary antibacterial agent with a wide antibacterial spectrum covering both gram-positive and gram-negative organisms. Urinary antibacterial activity can be shown within 30 minutes of administration.

The chemical structure of methenamine hippurate is such that a two-fold antibacterial action is obtained:

1. The slow release of the bactericidal formaldehyde, from the methenamine part, in the urine; acid pH is necessary for this reaction to occur. It is obtained and maintained there by the presence of hippuric acid.
2. The bacteriostatic effect of hippuric acid itself on urinary tract pathogens.

Methenamine hippurate is readily absorbed from the gastro-intestinal tract and excreted via the kidney.

Plasma concentrations of methenamine hippurate reach maximum 1-2 hours after a single dose and then decline with a half-life of about 4 hours. Methenamine recovered in the urine corresponds to about 80% of the dose given per 12 hours.

Non-clinical data reveal no special hazard for humans based on repeated dose toxicity studies. No carcinogenicity or genotoxicity data are available for methenamine hippurate. Methenamine did not demonstrate any carcinogenic potential in long term studies in rodents.

In limited studies in pregnant rabbits with methenamine hippurate at approximately 3 times the clinical dose based on body surface area, there was increased post-implantation loss resulting in lower litter sizes and a limited occurrence of fetal deformities including shortness of tail and malrotation of limbs. No effects on development were noted at doses equivalent to the clinical dose. Methenamine hippurate, administered at approximately 3 times the clinical dose, based on body surface area, did not adversely affect the fertility of female rats. Effects on male fertility have not been adequately studied.