ascorbic-acid and methenamine-hippurate

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

The effects of ammonium chloride, methenamine hippurate and ascorbic acid on urinary pH was studied in 14 normal subjects. A statistically significant reduction of urinary pH was recorded with ammonium chloride in daily doses of 1.5 and 3 g, but not with 2 g of methenamine hippurate or 1.8 g of ascorbic acid. Long-term treatment with ammonium chloride in doses between 1.5 and 3 g was given to 11 patients in order to reduce the risk of new stone formation or growth of fragments remaining after disintegration of infected renal stones. Biochemical stone analyses showed struvite in 9 of the treated stones, and urine cultures verified the presence of urease-producing bacteria in 10 patients. Apart from ammonium chloride, the patients were treated with antibiotics, in 4 patients continuously and in the others during periods from 2 to 34 months. The patients were followed for an average period of 32 months. No adverse reactions were recorded with the dosage used. Initially, 6 patients were stone-free, whereas 5 had residual stone fragments with a largest diameter ranging from 4 to 20 mm. At follow-up, 2 patients were still stone-free, and of 5 patients with residual fragments 1 showed stable disease and 3 an improved stone situation. In 5 patients, 3 of whom had residual stone fragments, antibiotic treatment had been interrupted without infectious relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Ammonium Chloride; Anti-Infective Agents, Urinary; Ascorbic Acid; Female; Hippurates; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Male; Methenamine; Middle Aged; Recurrence; Time Factors; Urinary Tract Infections; Urine

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