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At least 19 recordsLinked to original sources
PubMed1981

Urinary excretion of methenamine and formaldehyde: evaluation of 10 methenamine products in humans.

The urinary excretion of both methenamine and formaldehyde was measured for 48 hr after the oral administration of 10 different methenamine products to 10 human subjects in a crossover study. The following dosage forms were evaluated: a tablet of methenamine base, a methenamine hippurate tablet, and eight products containing methenamine mandelate, including six enteric-coated tablets, a suspension, and a granule dosage form. The nonenteric-coated dosage forms were absorbed more rapidly, based on maximum excretion rates that occurred within 3 hr after dosing. The enteric-coated tablets, which were designed not to release methenamine until reaching the intestinal tract, exhibited maximum excretion rates that did not occur until 7-17 hr after dosing. There were no significant differences (p greater than 0.05) among products in terms of total excretion of free formaldehyde in the urine. However, large differences (p less than 0.05) were noted among products for urinary recovery of total methenamine, with the amount of administered dose recovered ranging from 16 to 83%.

Adult↗
PubMedDate not supplied

Simultaneous determination of methenamine and formaldehyde in the urine of humans after methenamine administration.

Methenamine (hexamethylenetetramine) and its hydrolysis product formaldehyde are determined in the presence of each other in urine by a spectrophotometric method. Formaldehyde is assayed by a colour reaction with tryptophan, sulphuric acid and ferric chloride after precipitating methenamine by three treatments with mercuric chloride. Methenamine is indirectly analysed by hydrolysis to formaldehyde with dilute hydrochloric acid. Formaldehyde levels as low as 5.0 micrograms ml-1 in the presence of methenamine concentrations as high as 2.5 mg ml-1 can be assayed. Of practical significance is the feature that urine may be stored up to 1 weeks for analysis, by appropriate dilution and freezing, without excessive loss of methenamine or formaldehyde. The method was applied to the dtermination of the bioavailability of methenamine hippurate in ten human volunteers.

Biological Availability↗
PubMed1979

Drug therapy reviews: methenamine mandelate and methenamine hippurate.

The mechanism of action, spectrum of antimicrobial activity, pharmacokinetics, adverse effects, therapeutic use, and dosage of methenamine hippurate and methenamine mandelate are reviewed. The antimicrobial activity of methenamine depends on its conversion in the urine to formaldehyde. Formaldehyde's spectrum of antibacterial activity encompasses all urinary tract pathogens. Urinary concentrations of formaldehyde vary with pH and urine volume; however, there is no documentation that acdification of the urine enhances methenamine's therapeutic activity. Adverse reactions to methenamine, including gastrointestinal intolerance and skin reactions, are mild and reversible and occur infrequently. Methenamine mandelate and hippurate are effective in the prevention of recurrent urinary tract infections except in patients with Foley catheters or who require intermittent catheterization.

Bacteria↗
PubMed1979

Biological fate of methenamine in man. Absorption, renal excretion and passage to umbilical cord blood, amniotic fluid and breast milk.

Methenamine hippurate was administered orally as tablets or granules to healthy volunteers. Plasma concentrations of methenamine reached a maximum 1--2 hours after a single dose and then declined with a half-life of about 4 hours. The apparent distribution volume was similar to that of total body water. Renal clearance of methenamine was somewhat lower than that of creatinine. In cross-over experiments over six days, methenamine recovered in the urine corresponded to about 80 per cent of the dose given per 12 hours, slightly lower values being obtained from granules than from tablets. The efficient renal elimination of methenamine was confirmed in similar studies on patients post-operatively. Methenamine hippurate was also given to healthy pregnant women during labor, a few hours before expected delivery. Methenamine was found to pass the placental barrier. The concentration of methenamine in umbilical cord plasma was low but reached the level in maternal plasma after about 4 hours. In amniotic fluid the methenamine con centration was low and varying. No correlation was obtained to the maternal or umbilical cord plasma levels. The methenamine concentration in breast milk was of the same magnitude as in maternal plasma. It is concluded that methenamine may be safely given to pregnant and lactating women with respect to the ellbeing of the child.

Absorption↗
PubMed1986

Separation and quantitation of methenamine in urine by ion-pair extraction.

An ion-pair extraction technique is described for separating methenamine, a urinary tract antibacterial agent, from formaldehyde in human urine samples. Separation conditions are developed from extraction constants for the methenamine-bromocresol green ion-pair. The technique involves adsorption of the ion-pair onto a silica cartridge and elution with methylene chloride:1-pentanol (95:5). Methenamine is freed from the ion-pair by the addition of excess tetrabutylammonium iodide and converted to formaldehyde (determined spectrophotometrically) by reaction with ammonia and acetylacetone. Linear standard plots were obtained from urine containing methenamine which was diluted to 10-160 micrograms/mL. The lower limit of detection was 6 micrograms/mL of methenamine. Absolute recovery from urine was greater than or equal to 94.5%. The precision (CV) of detection of methenamine in the presence of formaldehyde was less than 2%, and less than or equal to 4.5% for the detection of formaldehyde in the presence of methenamine. No interferences were noted. The applicability of the method was demonstrated by analysis of human urine levels of both methenamine and formaldehyde following oral administration of a methenamine salt to a volunteer.

Adult↗
PubMed1984

Formaldehyde generation from methenamine salts in spinal cord injury.

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.

Anti-Infective Agents, Urinary↗
PubMedDate not supplied

Long-term treatment with methenamine hippurate in recurrent urinary tract infection.

Twenty-four patients with a history of recurrent urinary tract infection and in whom residual urine was considered to be a factor of importance for chronicity, have been treated for an average of 16 months with 1 g methenamine hippurate morning and evening. No patient had urinary calculus at the commencement of treatment and neither did any patient have an indwelling catheter. In patients without urinary tract infection or in whom abacteriuria was achieved with methenamine hippurate, the number of reinfections was reduced by approximately two thirds compared to periods prior to treatment. No patient was completely free from infection throughout the whole treatment period. However, in no case did bacteria with extensive resistance appear. When urinary tract infection was treated with methenamine hippurate, abacteriuria was achieved in only 6 of 14 patients. It would therefore seem that this agent is only of limited value for treatment of established infection. In the event of manifest infection it would appear appropriate to treat the infection primarily with antibiotics and to use methenamine hippurate for prophylaxis when abacteriuria has been achieved. No patient developed urinary calculus during treatment with methenamine hippurate and no deterioration of renal function or haematological change was observed.

Adult↗
PubMed1979

Appraisal of ascorbic acid for acidifying the urine of methenamine-treated geriatric patients.

A study was made of 73 elderly patients receiving methenamine and ascorbic acid concurrently. Each patient had an indwelling Foley catheter. Urinary pH was assessed in relation to the dosage of ascorbic acid, duration of therapy, formulation, and dosing intervals for ascorbic acid and methenamine. Statistical analysis revealed a significant increase in urinary pH when the dosage of ascorbic acid was increased. No significant relationships were found between urinary pH and the dosage forms of ascorbic acid, the salt of methenamine used, or the duration of methenamine therapy. Changes in urinary pH at different dosing intervals for ascorbic acid were found to be significant, at the 10 percent level only, for the three-times-daily dose schedule. These data raise a question as to the value of ascorbic acid for acidifying the urine of catheterized patients receiving methenamine therapy.

Aged↗
PubMed1987

Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study.

In a randomised, double blind, long term, crossover study 1 g twice daily of methenamine hippurate was compared with placebo for its preventive effect on recurrent attacks of acute cystitis. Methenamine hippurate and placebo were interchanged every six months for two years. During one of the years patients took 250 ml extra fluid every morning and evening. Out of 21 enrolled patients, 14 completed the first year and 13 both years of treatment, which permitted the evaluation of 27 patient years. There were 52 episodes of acute cystitis caused by reinfection: 41 occurred during placebo treatment and only 11 during the methenamine hippurate regimen (p less than 0.01). Extra fluid intake did not reduce the incidence of acute cystitis, nor did it reduce the effect of methenamine hippurate. Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics.

Acute Disease↗
PubMed1983

Conductometric determination of methenamine.

A method of conductometric titration for determination of methenamine is presented. An aqueous solution of silicotungstic acid is used as titrant. The acid and methenamine form an insoluble compound in which the molar ratio of the acid to methenamine is 1:4. Conductometric curves were obtained, the shapes of which are suitable for accurate and reproducible determination of the end point of titration. The results show reasonable accuracy. Good reproducibility was achieved even when small quantities of methenamine had to be determined.

Chemical Phenomena↗
PubMed1991

Decreased incidence of urinary tract infections in patients with spinal cord injury: effect of methenamine.

This study was designed to determine the effect of methenamine on the frequency of urinary tract infections (UTI) in hospitalized patients after spinal cord injury. The study included 56 patients with neurogenic bladder dysfunction treated with intermittent catheterization. A group of 34 patients was treated with methenamine, 1g twice daily; the other group of 22 patients was the control group receiving no antimicrobial therapy. On a weekly basis urine samples from all patients were obtained for urinalysis and culture. A total of 500 urine samples were analyzed. The patients treated with methenamine had 23.4% positive urine cultures which was significantly lower than 57.5% in the untreated control group (p less than 0.001). Our data suggest that methenamine therapy is an effective prevention of UTI in paralyzed patients with neurogenic bladder dysfunction during the rehabilitation in hospital.

Bacteriuria↗
PubMed1977

Lack of effect of methenamine in suppression of, or prophylaxis against, chronic urinary infection.

Methenamine is frequently prescribed for patients who have chronic urinary infection to suppress bacterial growth during active infection or to prevent recurrence once an infection has been brought under control. We have examined the effect of methenamine mandelate and ascorbic acid on bacteriuria in para- and quadriplegics from a spinal cord unit. Patients with indwelling urinary catheters and those on a program of intermittent catheterization were included. No suppressive or prophylactic effect of this regimen was observed in any of our patients. Methenamine does not appear to be an effective antimicrobial agent in subjects who have an indwelling urinary catheter or in patients with spinal cord injury who are on intermittent catheterization. Since there appears to be reason to question the efficacy of methenamine in situations in which it is usually prescribed, evidence should be sought for a therapeutic effect in other cases. If no benefit is observed, the drug should not be used.

Ascorbic Acid↗
PubMed1975

Topical methenamine therapy for hyperhidrosis.

Methenamine, in a gel stick formulation, effectively decreased palmar and plantar sweating in 24 of 26 individuals studied. All patients had essential hyperhidrosis and were evaluated in a double-blind, placebo-controlled study. Even though methenamine is believed to act by the slow release of formaldehyde, one patient, who had a formaldehyde sensitivity that was proved by a patch test, was able to use the methenamine gel stick without difficulty. Approximately one third of the patients experienced some continuing relief for one to three weeks after discontinuing the trial medication. I conclude that methenamine is a safe, effective addition to the available types of topical therapy for essential hyperhidrosis.

Administration, Topical↗
PubMed1984

Methenamine as an induced artifact during extraction of formaldehyde-preserved tissue.

The effect of different basic drug assay procedures on the formation of artifactual methenamine from formaldehyde preserved and nonpreserved tissue was studied. Trichloroacetic acid was compared with ammonium sulfate as a protein precipitant and sodium hydroxide was compared with ammonium hydroxide as a pH modifier. The assay of nonpreserved tissue failed to result in the detection of methenamine. However, when preserved tissue was assayed by procedures which utilized ammonium compounds, large quantities of methenamine were detected using TLC and GC/MS. Trace quantities of methenamine were detected in extracts of preserved autolyzed tissue which was assayed using nonammonium compounds.

Animals↗
PubMed1982

Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy.

Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one 1/day. Proteus vulgaris, Pseudomonas aeruginosa, and E. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters.

Aged↗