Page last updated: 2024-11-05

methenamine hippurate

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Methenamine hippurate is a urinary tract antiseptic used to treat urinary tract infections (UTIs). It is synthesized by reacting hexamethylenetetramine with hippuric acid. The compound is converted to formaldehyde in the acidic environment of the urine, which then inhibits the growth of bacteria. Methenamine hippurate is typically taken orally and is absorbed into the bloodstream. It is then excreted in the urine, where it exerts its antimicrobial effects. The compound is effective against a wide range of bacteria, including Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. It is often used to prevent UTIs in people who are prone to these infections, such as those with urinary catheters or a history of recurrent UTIs. Methenamine hippurate is generally well-tolerated, but it can cause side effects such as nausea, vomiting, and stomach pain. It is important to note that methenamine hippurate is not effective against all types of bacteria, and it should not be used to treat UTIs caused by resistant bacteria. Methenamine hippurate is a valuable treatment option for UTIs, but it is important to use it appropriately and under the guidance of a healthcare professional.'

methenamine hippurate: both parts of molecule contribute to its antibacterial action [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID21945
CHEMBL ID1201104
CHEBI ID6825
SCHEMBL ID3029
MeSH IDM0057805

Synonyms (54)

Synonym
hexamine hippurate
hexamethylene tetramine hippurate
einecs 227-206-5
hexamethylenetetramine monohippurate
hexamethylenetetramine hippurate
r-657
methenamine hippurate
n-benzoylglycine, compound with 1,3,5,7-tetraazatricyclo(3.3.1.13,7)decane (1:1)
viapta
methenamine hippurate [usan]
haiprex
hippramine
hiprex
urex (tn)
D00855
hiprex (tn)
methenamine hippurate (jan/usp)
5714-73-8
CHEMBL1201104
S9466
m329791l57 ,
methenamine hippurate [usan:usp:inn:ban]
unii-m329791l57
FT-0671059
methenamine hippurate [usp monograph]
methenamine hippurate [orange book]
methenamine hippurate [mart.]
methenamine hippurate [vandf]
methenamine hippurate [usp-rs]
methenamine hippurate [jan]
methenamine hippurate [usp impurity]
methenamine hippurate [who-dd]
SCHEMBL3029
CHEBI:6825
hexamethylenetetramine monohippurate;hexamethylenetetramine monohippurate
methenamine (hippurate)
HY-B1691
2-benzamidoacetic acid;1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane
mfcd00072147
n-[hydroxy(phenyl)methylidene]glycine--1,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane (1/1)
DTXSID10972603
CS-0013675
D81437
Q27283414
AS-57463
1,3,5,7-tetraazatricyclo[3.3.1.1(3),?]decane; 2-(phenylformamido)acetic acid
1,3,5,7-tetraazaadamantane benzoylglycinate
AKOS037645132
methenamine hippurate (usp monograph)
glycine, n-benzoyl, compound with 1,3,5,7-tetraazatricyclo(3.3.1.1(sup 3,7))decane(1:1)
methenamine hippurate (usp-rs)
methenamine hippurate (mart.)
methenamine hippurate (usan:usp:inn:ban)
methenamine hippurate (usp impurity)

Research Excerpts

Overview

Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis. It has the advantage of not inducing cross resistance to conventional antibiotics.

ExcerptReferenceRelevance
"Methenamine hippurate is a urinary antiseptic used as preventive treatment for recurrent urinary tract infections (UTIs) in some Scandinavian countries. "( Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU).
Åhrén, C; Godycki-Cwirko, M; Groen, WG; Grude, N; Gunnarsson, R; Heltveit-Olsen, SR; Hertogh, CMPM; Hoye, S; Koning, HAM; Kowalczyk, A; Lindbaek, M; Platteel, TN; Snaebjörnsson Arnljots, E; Sundvall, PD; Verheij, TJM, 2022
)
3.61
"Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics."( Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study.
Cronberg, S; Hellsten, S; Henriksson, L; Persson, KM; Stenberg, P; Welin, CO, 1987
)
1.26

Actions

ExcerptReferenceRelevance
"Methenamine hippurate seems to enhance barrier function as evidenced by decreased urothelial permeability and increased urinary IgA levels, without worsening inflammation. "( The Impact of Methenamine Hippurate Treatment on Urothelial Integrity and Bladder Inflammation in Aged Female Mice and Women With Urinary Tract Infections.
Chu, CM; Ligon, MM; Lowder, JL; McDaniel, K; Mora, A; Mysorekar, IU; Sawhill, JL, 2022
)
2.52

Toxicity

ExcerptReferenceRelevance
" Methenamine had few adverse side effects for patients."( Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study.
Ho, B; Hollyer, I; Ison, MG; Varias, F, 2019
)
0.82

Dosage Studied

ExcerptRelevanceReference
" No adverse reactions were recorded with the dosage used."( Long-term acidification of urine in patients treated for infected renal stones.
Tiselius, HG; Wall, I, 1990
)
0.28
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
N-acylglycineAn N-acyl-amino acid in which amino acid specified is glycine.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (2)

Assay IDTitleYearJournalArticle
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (55)

TimeframeStudies, This Drug (%)All Drugs %
pre-199024 (43.64)18.7374
1990's6 (10.91)18.2507
2000's5 (9.09)29.6817
2010's11 (20.00)24.3611
2020's9 (16.36)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 84.61

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index84.61 (24.57)
Research Supply Index4.38 (2.92)
Research Growth Index4.79 (4.65)
Search Engine Demand Index147.56 (26.88)
Search Engine Supply Index2.01 (0.95)

This Compound (84.61)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials21 (36.21%)5.53%
Reviews9 (15.52%)6.00%
Case Studies3 (5.17%)4.05%
Observational0 (0.00%)0.25%
Other25 (43.10%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (10)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Prospective Randomized Study to Compare Clinical Outcomes in Patients With Osteomyelitis Treated With Intravenous Antibiotics Versus Intravenous Antibiotics With an Early Switch to Oral Antibiotics [NCT02099240]Early Phase 111 participants (Actual)Interventional2014-03-06Terminated(stopped due to Not enough patient enrollment and lack of staffing)
Clinical Assessment of Urinary Antiseptics Methenamine and Methylthioninium in Recurrent Cystitis [NCT03379389]Phase 4284 participants (Actual)Interventional2018-03-31Completed
Methenamine Hippurate Versus Trimethoprim in the Prevention of Recurrent UTIs [NCT03077711]Phase 492 participants (Actual)Interventional2016-06-30Completed
Probiotics/Lactobacillus as a Prophylactic Aid in Recurrent Bacterial Cystitis in Women. A Randomized, Prospective, Double-Blinded, Placebo Controlled, Multi-Center Study. [NCT00781625]120 participants (Anticipated)Interventional2008-10-31Recruiting
The Efficacy and Cost-effectiveness of a 24-hour Course of metheNamine Hippurate for Preventing Post-Operative Urinary Tract Infection [NCT02358993]201 participants (Actual)Interventional2014-12-31Completed
Methenamine Hippurate With Cranberry Capsules Versus Cranberry Capsules Alone for UTI Prevention in a Short-term Indwelling Foley Catheter Population After Urogynecological Surgery: A Double-Blinded Randomized Controlled Trial [NCT03818321]Phase 2185 participants (Actual)Interventional2019-06-17Completed
A Multidisciplinary, Multimodal Bundled Care Approach to Chronic Pelvic Pain [NCT05658874]Phase 380 participants (Anticipated)Interventional2022-12-01Recruiting
Phase III, Prospective, Multicenter, Single-blind, Randomized, Superiority to Evaluate the Efficacy and Safety of Methenamine Association 250mg + Methylthioninium Chloride 20 mg Compared to Phenazopyridine 100 mg in Symptomatic Control of Dysuria [NCT01657448]Phase 3316 participants (Actual)Interventional2016-06-27Completed
The Efficacy and Effect of Methenamine Hippurate in a Non-antibiotic, Multimodal Approach to UTI Prevention [NCT03996057]Phase 40 participants (Actual)Interventional2018-06-20Withdrawn(stopped due to "Project canceled due to PI leaving institution, staff changes and COVID~Project canceled for other reason , describe: - Due to staff changes and COVID~Project canceled due to PI leaving, staff changes and COVID")
The Effect of Methenamine Hippurate to Reduce Antibiotic Prescribing Due to New Episodes of Urinary Tract Infections (UTI) in Elderly Women With Recurrent UTI - a Triple- Blinded, Randomized Placebo-controlled Phase IV Study [NCT04077580]Phase 4400 participants (Anticipated)Interventional2019-11-01Enrolling by invitation
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT02358993 (5) [back to overview]Antibiotic Resistance of Culture-positive Symptomatic UTI
NCT02358993 (5) [back to overview]Number of Participants With Culture-positive Symptomatic UTI
NCT02358993 (5) [back to overview]Rate of UTI Consistent With NHSN Criteria
NCT02358993 (5) [back to overview]Treatment of Clinically Suspected UTI - Per Protocol
NCT02358993 (5) [back to overview]Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis
NCT03077711 (5) [back to overview]Morisky Medication Adherence Survey
NCT03077711 (5) [back to overview]Number of Infections
NCT03077711 (5) [back to overview]Recurrent UTI
NCT03077711 (5) [back to overview]Time to Subsequent Infection as Defined From Time of Treatment Initiation to Recurrence of UTI
NCT03077711 (5) [back to overview]Bacterial Infection Prevalence and Types
NCT03818321 (1) [back to overview]Incidence of Urinary Track Infection (UTI)

Antibiotic Resistance of Culture-positive Symptomatic UTI

All patients who submit urine cultures that are positive will have sensitivities performed as per standard care. The prevalence of bacterial species and sensitivities will be collected (NCT02358993)
Timeframe: 3 weeks post-operative

InterventionParticipants (Count of Participants)
Methenamine0
Ciprofloxacin0

[back to top]

Number of Participants With Culture-positive Symptomatic UTI

All patients will be encouraged to submit urine cultures prior to treatment, but this is not always possible. Amongst patients who undergo urine culture as part of standard of care for UTI, the rate of positive cultures will be identified. (NCT02358993)
Timeframe: 3 weeks post-operative

InterventionParticipants (Count of Participants)
Methenamine5
Ciprofloxacin4

[back to top]

Rate of UTI Consistent With NHSN Criteria

We plan to analyze the prevalence of UTI in this population that meet the definitions of symptomatic UTI and catheter-associated UTI according to the National Healthcare Safety Network criteria. (NCT02358993)
Timeframe: 3 weeks post-operative

InterventionParticipants (Count of Participants)
Methenamine10
Ciprofloxacin6

[back to top]

Treatment of Clinically Suspected UTI - Per Protocol

This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills. (NCT02358993)
Timeframe: 3 weeks post-operative

InterventionParticipants (Count of Participants)
Methenamine12
Ciprofloxacin12

[back to top]

Treatment of Clinically Suspected UTI - Using Intent to Treat Analysis

This is defined as any symptomatic UTI requiring treatment with antibiotics as determined by the development of 2 or more of the following symptoms, in the absence of vaginal symptoms: urinary frequency; urinary urgency; dysuria; fever over 38oC/100.4oF; suprapubic, flank, or back pain; and/or chills. (NCT02358993)
Timeframe: 3 weeks post-operative

InterventionParticipants (Count of Participants)
Methenamine13
Ciprofloxacin12

[back to top]

Morisky Medication Adherence Survey

Morisky Medication Adherence Scale-8 (MMAS-8). Patient tolerability of medications using a tolerability survey. Minimum and maximum scores are 0 and 8 respectively. 0 means no adherence and 8 is maximal adherence. Low adherence corresponds to a score less than 6, medium adherence is between 6 and <8, and 8 is high adherence. (NCT03077711)
Timeframe: up to 12 months

Interventionunits on a scale (Mean)
Patients With Recurrent UTIs Arm 17.28
Patients With Recurrent UTIs Arm 26.94

[back to top]

Number of Infections

The number of infections at a 12 month follow up time period as defined by symptoms and positive urine culture. (NCT03077711)
Timeframe: up to 12 months

Interventionurinary tract infections (Mean)
Patients With Recurrent UTIs Arm 11.5
Patients With Recurrent UTIs Arm 21.6

[back to top]

Recurrent UTI

The number of patient who had a recurrence of UTI within 12 months (NCT03077711)
Timeframe: up to 12 months

InterventionParticipants (Count of Participants)
Patients With Recurrent UTIs Arm 128
Patients With Recurrent UTIs Arm 228

[back to top]

Time to Subsequent Infection as Defined From Time of Treatment Initiation to Recurrence of UTI

Patients will be advised to follow up with any symptoms of a recurrence or at 6 and 12 month intervals if symptom-free. (NCT03077711)
Timeframe: up to 12 months

Interventiondays (Mean)
Patients With Recurrent UTIs Arm 1101
Patients With Recurrent UTIs Arm 2119

[back to top]

Bacterial Infection Prevalence and Types

Urine cultures and sensitivities for positive urine cultures (NCT03077711)
Timeframe: up to 12 months

,
Interventioninfections (Number)
Escherichia coliKlebsiella pneumoniaEnterococcus faecalisExtended spectrum beta lactamase Escherichia coliOther bacteriaStrains pan sensitive to all antibioticsStrains resistant to trimethoprimStrains resistant to abx other than trimethoprim
Patients With Recurrent UTIs Arm 14311361555810
Patients With Recurrent UTIs Arm 25069912203029

[back to top]

Incidence of Urinary Track Infection (UTI)

Incidence of UTIs will be diagnosed at one week post-op visit. (NCT03818321)
Timeframe: From surgery to one week post-op visit, approximately 1 week post surgery

InterventionParticipants (Count of Participants)
Methenamine Hippurate With Cranberry62
Placebo With Cranberry71

[back to top]