Penetration of Moxifloxacin into Peripheral Compartments in Humans

ABSTRACT To characterize the penetration of moxifloxacin (BAY 12-8039) into peripheral target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, an innovative clinical sampling technique. In addition, moxifloxacin concentrations were measured in cantharides-induced skin blisters, saliva, and capillary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in an open randomized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min. An almost-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed, with mean area under the concentration-time curve (AUC)interstitial fluid/AUCtotal-plasma ratios ranging from 0.38 to 0.55 and mean AUCinterstitial fluid/AUCfree-plasma ratios ranging from 0.81 to 0.86. The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h, indicating a preferential penetration of moxifloxacin into inflamed lesions. The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels in plasma. Our data show that moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90% of isolates are inhibited for most clinically relevant bacterial strains, notably including penicillin-resistant Streptococcus pneumoniae. These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans.

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Target Site Concentrations of Ciprofloxacin after Single Intravenous and Oral Doses

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.12.3724-3730.2002 ◽

2002 ◽

Vol 46 (12) ◽

pp. 3724-3730 ◽

Cited By ~ 49

Author(s):

Martin Brunner ◽

Heino Staβ ◽

Jan-Georg Möller ◽

Claudia Schrolnberger ◽

Boban Erovic ◽

...

Keyword(s):

Skeletal Muscle ◽

Interstitial Fluid ◽

Soft Tissues ◽

Interstitial Space ◽

Target Site ◽

Crossover Fashion ◽

Bacterial Strains ◽

Concentration Time

ABSTRACT To characterize the potential of ciprofloxacin penetration into human soft tissues following intravenous (i.v.) and oral (p.o.) administration, we measured the free ciprofloxacin concentrations in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue by microdialysis. In addition, ciprofloxacin concentrations were measured in cantharis-induced skin blisters, saliva, and capillary plasma and were compared to the total concentrations in venous plasma. Furthermore, a pharmacodynamic in vitro model was used to simulate in vivo pharmacokinetics in bacterial culture. Eight healthy volunteers received ciprofloxacin in an open randomized crossover fashion either as a single i.v. infusion of 400 mg over 60 min or as a single p.o. dose of 500 mg. For both tissues the mean areas under the concentration-time curves (AUCs) for interstitial space fluid (AUCinterstitial fluids) were significantly lower than the corresponding AUCplasmas, with AUCinterstitial fluid/AUCplasma ratios ranging from 0.38 to 0.68. For skeletal muscle, the AUCinterstitial fluid was significantly higher after administration of 400 mg i.v. than after administration of 500 mg p.o., with a ratio of the AUC after p.o. administration/AUC after i.v. administration of 0.64. The ratio of the concentration in skeletal muscle/concentration in plasma increased over the entire observation period, implying that ciprofloxacin concentrations were not at steady state. The ratio of the concentration in skin blister fluid/concentration in plasma reached values above 4, indicating a preferential penetration of ciprofloxacin into inflamed lesions. The concentrations in saliva and capillary blood were similar to the corresponding total levels in plasma. In vitro both in vivo ciprofloxacin concentration-time profiles were equally effective against select bacterial strains. In conclusion, single-dose administration of two bioequivalent dosage forms of ciprofloxacin might lead to differences in target site pharmacokinetics. These differences, however, are not related to a difference in target site pharmacodynamics.

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Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum β-Lactamase-Producing Escherichia coli with Canine Ex Vivo Modeling: A Pilot Study

Antibiotics ◽

10.3390/antibiotics9050230 ◽

2020 ◽

Vol 9 (5) ◽

pp. 230

Author(s):

Kazuki Harada ◽

Takae Shimizu ◽

Koji Kawaguchi ◽

Takeshi Furuhashi ◽

Genki Ishihara

Keyword(s):

Escherichia Coli ◽

Drug Administration ◽

Ex Vivo ◽

Area Under The Curve ◽

Urine Concentration ◽

Test Period ◽

Time Curve ◽

Extended Spectrum ◽

Drug Concentrations ◽

Tract Infections

Fosfomycin is a candidate drug for extended-spectrum β-lactamase (ESBL)-producing bacteria, but its efficacy is yet to be investigated in dogs. This study investigated the urinary pharmacokinetic/pharmacodynamic (PK/PD) profile of fosfomycin orally administered at 80 mg/kg to six healthy dogs to assess its efficacy for canine urinary tract infections (UTIs) caused by ESBL-producing bacteria. Four strains of ESBL-producing Escherichia coli (ESBL-EC) characterized by fosfomycin minimum inhibitory concentrations (MICs) of 0.5, 1, 2, and 32 µg/mL were used. Urine samples for the measurement of urinary drug concentrations and urinary bactericidal titers (UBTs) were obtained after drug administration. The urinary concentrations (µg/mL, mean ± SE) were 1348.2 ± 163.5, 1191.6 ± 260.2, and 661.1 ± 190.4 at 0–4, 4–8, and 8–12 h, respectively, after drug administration. The mean urinary area under the curve during the test period (AUC0–12) of fosfomycin was estimated to be 12,803.8 µg·h/mL. The UBTs for all tested strains fluctuated closely with urine concentration during the test period (r = 0.944–1.000), and the area under the UBT-versus-time curve correlated with the urinary AUC/MIC of each strain (r = 0.991). According to the optimal urinary PK/PD target value, fosfomycin at 80 mg/kg twice daily may be suitable for the treatment of canine UTIs caused by ESBL-EC presenting MIC ≤ 128 µg/mL.

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Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.10.2728-2732.2000 ◽

2000 ◽

Vol 44 (10) ◽

pp. 2728-2732 ◽

Cited By ~ 65

Author(s):

Martin Frossard ◽

Christian Joukhadar ◽

Boban M. Erovic ◽

Peter Dittrich ◽

Paulus E. Mrass ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissues ◽

Pharmacokinetic Profile ◽

Interstitial Space ◽

Soft Tissue Infections ◽

Time Curve ◽

Tract Infections ◽

High Degree

ABSTRACT Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (n = 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC0–8muscle )/AUC0–8serum of 0.48 ± 0.08 and 0.53 ± 0.04 and ratios of AUC0–8adipose tissue /AUC0–8serum of 0.74 ± 0.12 and 0.71 ± 0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus,Enterobacter cloacae, and Serratia marcescensfor which MICs were 16 μg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

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Clinical Pharmacokinetics of Meropenem and Biapenem in Bile and Dosing Considerations for Biliary Tract Infections Based on Site-Specific Pharmacodynamic Target Attainment

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00497-11 ◽

2011 ◽

Vol 55 (12) ◽

pp. 5609-5615 ◽

Cited By ~ 10

Author(s):

Kazuro Ikawa ◽

Akira Nakashima ◽

Norifumi Morikawa ◽

Kayo Ikeda ◽

Yoshiaki Murakami ◽

...

Keyword(s):

Biliary Tract ◽

Drug Concentration ◽

Venous Blood ◽

Target Attainment ◽

Time Curve ◽

Clinical Pharmacokinetics ◽

Site Specific ◽

Content Type ◽

Drug Concentrations ◽

Tract Infections

ABSTRACTThe present study investigated the pharmacokinetics of meropenem and biapenem in bile and estimated their pharmacodynamic target attainment at the site. Meropenem (0.5 g) or biapenem (0.3 g) was administered to surgery patients (n= 8 for each drug). Venous blood samples and hepatobiliary tract bile samples were obtained at the end of infusion (0.5 h) and for up to 5 h thereafter. Drug concentrations in plasma and bile were analyzed pharmacokinetically and used for a Monte Carlo simulation to predict the probability of attaining the pharmacodynamic target (40% of the time above the MIC). Both drugs penetrated similarly into bile, with mean bile/plasma ratios of 0.24 to 0.25 (maximum drug concentration) and 0.30 to 0.38 (area under the drug concentration-time curve). The usual regimens of meropenem (0.5 g every 8 h [q8h]) and biapenem (0.3 g q8h) (0.5-h infusions) achieved similar target attainment probabilities in bile (≥90%) againstEscherichia coli,Klebsiella pneumoniae, andEnterobacter cloacaeisolates. However, againstPseudomonas aeruginosaisolates, meropenem at 1 g q8h and biapenem at 0.6 g q8h were required for values of 80.7% and 71.9%, respectively. The biliary pharmacodynamic-based breakpoint (the highest MIC at which the target attainment probability in bile was ≥90%) was 1 mg/liter for 0.5 g q8h and 2 mg/liter for 1 g q8h for meropenem and 0.5 mg/liter for 0.3 g q8h and 1 mg/liter for 0.6 g q8h for biapenem. These results help to define the clinical pharmacokinetics of the two carbapenems in bile while also helping to rationalize and optimize the dosing regimens for biliary tract infections based on site-specific pharmacodynamic target attainment.

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1115. Evaluation of Gepotidacin (GSK2140944) Pharmacokinetics and Food Effect in Japanese Subjects

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1309 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S650-S651

Author(s):

Mohammad Hossain ◽

Courtney Tiffany ◽

Aline Barth ◽

Aparna Raychaudhuri ◽

Etienne F Dumont

Keyword(s):

Tolerability Profile ◽

Time Curve ◽

Fed State ◽

Fasted State ◽

Drug Concentrations ◽

Tract Infections ◽

Oral Doses ◽

Japanese Subjects

Abstract Background Gepotidacin, a novel, first-in-class triazaacenaphthylene antibiotic, inhibits bacterial replication and has in vitro and in vivo activity against key pathogens, including drug-resistant strains, associated with a range of infections. Gepotidacin is currently in Phase 3 clinical studies for the treatment of uncomplicated urinary tract infections and gonorrhea. This study (NCT02853435) was designed to assess gepotidacin pharmacokinetics (PK) in Japanese subjects (fasted and fed). Methods A tablet formulation of 750 mg gepotidacin free base was used in the study, which was conducted in two parts: Part 1, gepotidacin PK was assessed following 1500 and 3000 mg single oral doses in the fasted state; and Part 2, gepotidacin PK was assessed following 1500, 2250, and 3000 mg single oral doses in the fed state. Serial blood and urine samples were collected in both study parts. Results Part 1: The area under the plasma drug concentration-time curve from time 0 to infinity (AUC[0–∞]) and maximum observed concentration (Cmax) were slightly higher in Japanese subjects than in Caucasian subjects at the same dose levels and with the same formulation. Following gepotidacin dosing in the fasted state, the 1500 mg dose was tolerated, while the 3000 mg dose was poorly tolerated with mild or moderate gastro-intestinal adverse effects (GI AEs) reported by most subjects shortly after being dosed. Part 2: PK was linear with doses in the range of 1500–3000 mg. Administration of gepotidacin 3000 mg tablets in the fed state slightly reduced Cmax and slightly increased AUC at the 3000 mg dose level. The 1500 and 2250 mg doses were tolerated while the 3000 mg dose was better tolerated compared to the fasted state with fewer and short-lived GI AEs, mostly mild in intensity. After oral administration of 1500–3000 mg, high urine drug concentrations were achieved, remaining above the minimum inhibitory concentration of 4 μg/mL for up to 24 hours. Conclusion The PK of gepotidacin following administration of a single oral dose to Japanese subjects was linear from 1500–3000 mg and food decreased Cmax without impact on exposure (AUC). Administration of gepotidacin with food resulted in an improved GI tolerability profile at the higher dose tested in Japanese subjects. Disclosures Mohammad Hossain, PhD, GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and past/current shareholder in GlaxoSmithKline plc.) Courtney Tiffany, BSc, GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and past/current shareholder in GlaxoSmithKline plc.) Aline Barth, MSC;PHD, GlaxoSmithKline plc. (Employee, Shareholder, Employee of and shareholder in GlaxoSmithKline plc.) Aparna Raychaudhuri, Ph.D., GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and past/current shareholder in GlaxoSmithKline plc.) Etienne F. Dumont, MD, GlaxoSmithKline plc. (Employee, Shareholder, Former employee of and shareholder in GlaxoSmithKline plc.)

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The Incidence of Overactive Bladder (OAB) in KIA Poly Patients at Pauh Health Center in Padang City Using Overactive Bladder Symptoms Score (OABSS)

JOURNAL OBGIN EMAS ◽

10.25077/aogj.3.2.55-62.2019 ◽

2019 ◽

Vol 3 (2) ◽

pp. 55-62

Author(s):

Bobby Indra Utama ◽

Widayat Widayat ◽

Berriandi Arwan

Keyword(s):

Urinary Incontinence ◽

Overactive Bladder ◽

Health Center ◽

Sampling Technique ◽

Reproductive Age ◽

Exclusion Criteria ◽

Symptom Scores ◽

Bladder Symptom ◽

Bladder Symptoms ◽

Tract Infections

Objective : This study looked at the incidence of overactive bladder (OAB) in KIA poly patients at Pauh Health Center in Padang City using Overactive Bladder Symptomps Score (OABSS).Method : This research is descriptive. The sampling technique was purposive sampling by considering inclusion and exclusion criteria. The inclusion criteria were women of ideal reproductive age (20-35 years) who had given birth spontaneously, were not pregnant, did not suffer from neurological disorders, diabetes, post bladder surgery and or urinary tract infections and were not treated with Overactive Bladder (OAB), while the exclusion criteria are not willing to take part in the study. The study was carried out at the KIA Poly of Pauh City Health Center in Padang during January 2019. The variable in this study was Overactive Bladder (OAB).Result : In this study, 97.22% of respondents experienced complaints of overactive bladder (OAB), (97.14%) experienced an urgent complaint, and only a small percentage (2.86%) of respondents experienced urinary incontinence. The results of this study indicate that respondents who did not experience complaints of overactive bladder (OAB) were respondents with the smallest parity (parity 1).Conclusion : Most respondents experienced complaints of overactive bladder (OAB) and urgency, and only a small proportion of respondents experienced urinary incontinence. The results of this study indicate that respondents who did not experience complaints of overactive bladder (OAB) were respondents with the smallest parity (parity 1).Keywords : overactive bladder (OAB), Urgensi,inkontinensia urin, Overactive Bladder Symptom Scores (OABSS).

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1304. Characterization of Tebipenem Pivoxil Hydrobromide Pharmacokinetics-Pharmacodynamics (PK-PD) in a Neutropenic Murine Acute Pyelonephritis (AP) Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1487 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S666-S666

Author(s):

Brian D VanScoy ◽

Steven Fikes ◽

Christopher M Rubino ◽

Sujata M Bhavnani ◽

Nicole S Cotroneo ◽

...

Keyword(s):

Acute Pyelonephritis ◽

Free Drug ◽

Research Support ◽

Model Free ◽

Drug Concentrations ◽

Drug Plasma ◽

Dose Ranging ◽

Tebipenem Pivoxil ◽

Tract Infections ◽

The Relationship

Abstract Background Tebipenem pivoxil hydrobromide (tebipenem HBr), an orally (PO) bioavailable prodrug of tebipenem, is a carbapenem with broad-spectrum activity against Gram-positive and -negative bacteria that is being developed for the treatment of patients with complicated urinary tract infections, including AP. Data from a one-compartment in vitro infection model demonstrated that the ratio of free-drug plasma area under the curve (AUC) to MIC with adjustment for dosing interval (τ) (AUC:MIC ratio•1/τ) was the PK-PD index most associated with tebipenem HBr efficacy [VanScoy BD et al., IDWeek 2019, Poster 1565]. Studies were undertaken to characterize the magnitude of tebipenem HBr free-drug plasma AUC:MIC ratio•1/τ associated with efficacy for Enterobacteriaceae using a neutropenic murine AP model. Methods A single dose pharmacokinetic study was completed in neutropenic mice infected via intra-renal injection with 104 CFU/kidney of Escherichia coli NCTC 13441. Following PO administration of 4 tebipenem HBr doses (1, 15, 45 and 100 mg/kg), plasma samples were collected at 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-treatment initiation and drug concentrations were determined using LC/MS/MS. Dose-ranging studies were completed using a panel of 7 Enterobacteriaceae isolates (tebipenem HBr MIC values of 0.015 to 0.5 mg/L). Mice were infected with 104 CFU/kidney via intra-renal injection. Two hours post-incubation, 8 total daily tebipenem HBr doses (0.3 to 135 mg/kg) were fractionated into regimens given every 8 hours. The relationship between change in log10 CFU/g from baseline at 24 hours and free-drug plasma AUC:MIC ratio•1/τ was fit using a Hill-type model. Free-drug plasma AUC:MIC ratio•1/τ values associated with net bacterial stasis and 1- and 2-log10 CFU/g reductions from baseline at 24 hours were determined. Results The relationship between change in log10 CFU/g from baseline at 24 hours and tebipenem HBr free-drug plasma AUC:MIC ratio•1/τ described the data well (r2 = 0.833). Free-drug plasma AUC:MIC ratio•1/τ values associated with net bacterial stasis and a 1-log10 CFU/g reduction from baseline were 26.2 and 54.1, respectively. A 2-log10 CFU/g reduction was not achieved. Relationship between change in log10 CFU/g from baseline at 24 hours and tebipenem HBr free-drug plasma AUC:MIC ratio•1/τ based on data for a panel of Enterobacteriaceae isolates evaluated in the dose-ranging studies conducted using a neutropenic murine acute pyelonephritis model Conclusion These data will be useful to support tebipenem HBr dose selection for clinical studies in patients with AP. Disclosures Brian D. VanScoy, B.S., Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Steven Fikes, BA, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Christopher M. Rubino, PharMD, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Sujata M. Bhavnani, PharMD, MS, FIDSA, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Nicole S. Cotroneo, BS, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, PhD, Spero Therapeutics (Employee, Shareholder) Thomas R. Parr, PhD, Spero Therapeutics (Employee, Shareholder) Paul G. Ambrose, PharMD, FIDSA, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support)

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In Vitro Coliform Resistance to Bioactive Compounds in Urinary Infection, Assessed in a Lab Catheterization Model

Applied Sciences ◽

10.3390/app11094315 ◽

2021 ◽

Vol 11 (9) ◽

pp. 4315

Author(s):

Emanuel Vamanu ◽

Laura Dorina Dinu ◽

Cristina Mihaela Luntraru ◽

Alexandru Suciu

Keyword(s):

Urinary Tract ◽

Bioactive Compounds ◽

Urinary Tract Infections ◽

Antimicrobial Effect ◽

Biologically Active ◽

Bacterial Strains ◽

E Coli ◽

Functional Product ◽

Tract Infections

Bioactive compounds and phenolic compounds are viable alternatives to antibiotics in recurrent urinary tract infections. This study aimed to use a natural functional product, based on the bioactive compounds’ composition, to inhibit the uropathogenic strains of Escherichia coli. E. coli ATCC 25922 was used to characterize the IVCM (new in vitro catheterization model). As support for reducing bacterial proliferation, the cytotoxicity against a strain of Candida albicans was also determined (over 75% at 1 mg/mL). The results were correlated with the analysis of the distribution of biologically active compounds (trans-ferulic acid-268.44 ± 0.001 mg/100 g extract and an equal quantity of Trans-p-coumaric acid and rosmarinic acid). A pronounced inhibitory effect against the uropathogenic strain E. coli 317 (4 log copy no./mL after 72 h) was determined. The results showed a targeted response to the product for tested bacterial strains. The importance of research resulted from the easy and fast characterization of the functional product with antimicrobial effect against uropathogenic strains of E. coli. This study demonstrated that the proposed in vitro model was a valuable tool for assessing urinary tract infections with E. coli.

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Effect of Hydrolysable Tannins and Anthocyanins on Recurrent Urinary Tract Infections in Nephropathic Patients: Preliminary Data

Nutrients ◽

10.3390/nu13020591 ◽

2021 ◽

Vol 13 (2) ◽

pp. 591 ◽

Cited By ~ 1

Author(s):

Annalisa Noce ◽

Francesca Di Daniele ◽

Margherita Campo ◽

Manuela Di Lauro ◽

Anna Pietroboni Zaitseva ◽

...

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Bacterial Flora ◽

Bioactive Compound ◽

In Vitro Tests ◽

Bacterial Strains ◽

Quercetin Derivatives ◽

Hydrolysable Tannins ◽

Tract Infections

Urinary tract infections (UTIs) are caused by uropathogenic microorganism colonization. UTIs often require an antibiotic therapy that can cause the selection of antibiotic-resistant bacterial strains. A natural bioactive compound may represent a valid therapeutic adjuvant approach, in combination with drug therapy. In this paper, we present a pilot study, based on the administration of an oral food supplement (OFS), containing chestnut tannins and anthocyanins, to nephropathic patients suffering from recurrent UTIs (16 treated patients with 1 cp/day and 10 untreated patients). We performed laboratory tests and quality of life and body composition assessments, at T0 (baseline) and T1 (after 6 weeks OFS assumption). The analysis of OFS was performed by HPLC-DAD-MS for its content in polyphenols and by in vitro tests for its antioxidative and anti-free radical activities. In each capsule, polyphenol content was 6.21 mg (4.57 mg hydrolysable tannins, 0.94 mg anthocyanosides, 0.51 mg proanthocyanidins, 0.18 mg quercetin derivatives). A significant reduction of erythrocyte sedimentation rate was observed only in male patients. Urinalysis showed a significant reduction of leukocytes in both genders, whereas urinary bacterial flora at T1 significantly decreased only in male subjects. Tannins seem to exert an antimicrobial action according to gender, useful to counteract the recurrence of UTIs.

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