ascorbic-acid and methenamine-mandelate

The kinetics of conversion of methenamine to the active form formaldehyde were studied in pooled urine samples at 37 degrees in the pH range 4.9-6.5. Using a method for the determination of both formaldehyde and unhydrolyzed methenamine, the rate of formaldehyde formation in urine was found to be apparent first order and was pH dependent. Bactericidal concentrations of formaldehyde (> 28 micrograms ml-1) were achieved in 3 h in urine of pH 6.0 containing methenamine at 750 micrograms ml-1. There was no difference in the in vitro rate of conversion of methenamine to formaldehyde between the urine collected from normal subjects and the urine from subjects administered ascorbic acid. The rates of degradation of the mandelate and hippurate salts in buffer systems of various pH values did not differ significantly from those of methenamine base in urine adjusted to the same pH. The half-life of methenamine conversion to formaldehyde increased approximately 20 times from 20 h at pH 5.0 to about 400 h at pH 6.5. The data suggest that unless the urine is maintained below pH 6 only a small fraction of methenamine would be converted daily to formaldehyde and, thus, may explain the need for large doses of this drug in patients.

Topics: Anti-Infective Agents, Urinary; Ascorbic Acid; Formaldehyde; Hippurates; Humans; Hydrogen-Ion Concentration; Hydrolysis; In Vitro Techniques; Mandelic Acids; Methenamine

To achieve effective suppression of bacteriuria in spinal cord injured (SCI) patients, methenamine mandelate and methenamine hippurate are commonly given with ascorbic acid. Since the effectiveness of ascorbic acid as a urinary acidifier has been challenged and as it also has been suggested that methenamine salts do not produce effective urine formaldehyde concentrations in patients with indwelling urethral catheters, we studied two groups of SCI patients to determine (1) the effect of ascorbic acid on urine pH and formaldehyde concentration when administered with methenamine salts; (2) the effect of an indwelling urethral catheter versus intermittent catheterization on formaldehyde concentration in the urine of SCI patients taking methenamine salts; and (3) the relative urine formaldehyde concentrations produced by treatment with methenamine mandelate and methenamine hippurate in SCI patients. Methenamine mandelate produced significantly higher urine formaldehyde concentrations than did methenamine hippurate, especially among patients with intermittent catheterization. Ascorbic acid produced a significant effect on urine pH but not on formaldehyde concentration.

Topics: Anti-Infective Agents, Urinary; Ascorbic Acid; Bacteriuria; Formaldehyde; Hippurates; Humans; Hydrogen-Ion Concentration; Mandelic Acids; Methenamine; Spinal Cord Injuries

Topics: Acid-Base Equilibrium; Adult; Ammonium Chloride; Ascorbic Acid; Female; Fruit; Humans; Male; Mandelic Acids; Methenamine; Methionine; Middle Aged; Urine

Topics: Anti-Infective Agents, Urinary; Ascorbic Acid; Humans; Hydrogen-Ion Concentration; Mandelic Acids; Methenamine; Spinal Cord Injuries