Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 μg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2β: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.

• Klíčová slova
• Flavonoid, Isorhamnetin, Pharmacokinetics, Quercetin, Solid dispersion, Solubility,
• MeSH
• benzalkoniové sloučeniny farmakokinetika   chemie   MeSH
• intravenózní podání * MeSH
• krysa rodu Rattus MeSH
• potkani Wistar MeSH
• povidon * chemie   MeSH
• quercetin * farmakokinetika   analogy a deriváty   aplikace a dávkování   chemie   MeSH
• rozpustnost * MeSH
• voda * chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 3-methylquercetin MeSH Prohlížeč
• benzalkoniové sloučeniny MeSH
• povidon * MeSH
• quercetin * MeSH
• voda * MeSH

Benzalkonium chloride (BAK) compounds are commonly used in topical ophthalmic products as preservatives and stabilizers. BAK mixtures containing several compounds with different alkyl chain lengths are typically used. However, in chronic eye conditions, such as dry eye disease and glaucoma, the accumulation of adverse effects of BAKs was observed. Hence, preservative-free eye drops formulations are preferred. On the other hand, selected long-chain BAKs, particularly cetalkonium chloride, exhibit therapeutic functions, promoting epithelium wound healing and tear film stability. Nevertheless, the mechanism of BAKs influence on the tear film is not fully understood. By employing in vitro experimental and in silico simulation techniques, we elucidate the action of BAKs and demonstrate that long-chain BAKs accumulate in the lipid layer of the tear film model, stabilizing it in a concentration-dependent fashion. In contrast, short-chain BAKs interacting with the lipid layer compromise the tear film model stability. These findings are relevant for topical ophthalmic drug formulation and delivery in the context of selecting proper BAK species and understanding the dose dependency for tear film stability.

• Klíčová slova
• Benzalkonium chloride, Lipid films, Molecular dynamics, Tear film, Tear film lipid layer, Topical ophthalmic formulations,
• MeSH
• benzalkoniové sloučeniny škodlivé účinky   MeSH
• konzervační prostředky farmaceutické * farmakologie   MeSH
• lidé MeSH
• lipidy farmakologie   MeSH
• oční roztoky MeSH
• slzy MeSH
• syndromy suchého oka * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzalkoniové sloučeniny MeSH
• konzervační prostředky farmaceutické * MeSH
• lipidy MeSH
• oční roztoky MeSH

PURPOSE: The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent. METHODS: 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients). RESULTS: The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important. CONCLUSION: This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.

• MeSH
• antihypertenziva aplikace a dávkování   MeSH
• aplikace lokální MeSH
• benzalkoniové sloučeniny aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• fluorofotometrie MeSH
• glaukom s otevřeným úhlem farmakoterapie   MeSH
• hyperemie chemicky indukované   prevence a kontrola   MeSH
• konzervační prostředky farmaceutické aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nemoci spojivky chemicky indukované   prevence a kontrola   MeSH
• nitrooční tlak účinky léků   MeSH
• oční hypertenze farmakoterapie   MeSH
• oční roztoky MeSH
• polymery aplikace a dávkování   škodlivé účinky   MeSH
• prostaglandiny F syntetické aplikace a dávkování   MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antihypertenziva MeSH
• benzalkoniové sloučeniny MeSH
• konzervační prostředky farmaceutické MeSH
• oční roztoky MeSH
• polymery MeSH
• polyquaternium 1 MeSH Prohlížeč
• prostaglandiny F syntetické MeSH

The author calculated the daily dose of Benzalkonium Chloride (BAC) in eye drops used in glaucoma treatment from the patients point of view, which means the real amount of BAC applied in the conjunctival sac. The information about BAC concentration in 1 milliliter (mL) do not offer sufficient picture about real circumstances, because the size of the drop, especially after the introducing of the use of generic products in clinical practice in specific anti-glaucomatic drugs, differs significantly. The daily dose of BAC may have substantial significance in the patients treatment tolerance. The overview of BAC daily dose in single therapeutic groups and drugs follows: betablockers: Timo-COMOD 0, Arutimol 2.6, Vistagan 2.8, Timolol-POS 3.0, Arteoptic 3.7, Betoptic S 4.8, Timoptol MSD 6.3, Betoptic 10.0; alpha-mimetics: Alphagan 3.5, Luxfen 3.5, Aruclonin 7.1; derivates of prostaglandine, prostamides: Taflotan 0, Monopost 0, Lumigan 1.4, Unilat 3.1, Travatan 3.9, Latanoprost Apotex 4.3, Rescula 5.8, Latanoprost POS 5.9, Xalatan 6.0, Latanoprost Ratiopharm 6.0, Latanoprost Actavis 6.0, Latanoprost Arrow 6.0, Arulatan 5.4, Latalux 6.0, Glaucotens 6.0, Xaloptic 6.0, Solusin 6.1; carboanhydrase inhibitors: Batidor 3.8, Azopt 4.8, Trusopt 5.4, Oftidor 8.1; fixed combinations: Ganfort 1.4, Dorzolamid/timolol TEVA 2.8, Combigan 3.2, Duotrav 4.3, Cosopt 5.6, Xalacom 6.0, Glaucotima 6.0, Latanoprost/timolol Apotex 6.3, Azarga 6.4, Dorzogen Combi 6.5, and Dozotima 8.8 µl.

• MeSH
• antihypertenziva aplikace a dávkování   MeSH
• benzalkoniové sloučeniny aplikace a dávkování   MeSH
• glaukom farmakoterapie   patofyziologie   MeSH
• konzervační prostředky farmaceutické aplikace a dávkování   MeSH
• lidé MeSH
• nitrooční tlak účinky léků   MeSH
• oční roztoky MeSH
• příprava léků MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antihypertenziva MeSH
• benzalkoniové sloučeniny MeSH
• konzervační prostředky farmaceutické MeSH
• oční roztoky MeSH

Interaction of hyaluronan (NaHy) with the quaternary salt, benzalkonium chloride (BAC), was studied. Based on the DLS experiments, viscometry and surface tension measurements executed on hyaluronan samples with two molecular weights of Mw=1.8 MDa and Mw=0.35 MDa, the hypothesis was proposed suggesting that at certain BAC concentrations, hyaluronan can form aggregates, which lead to increase of the polymer coil size measured as z-average diameter. Moreover, it was confirmed that within the whole range of BAC concentrations, repeated variations in size and conformations of polymer coils occur, being connected with the critical micellar concentration of BAC and with hydrophobic interactions of non-polar segments of BAC with hyaluronan hydrophobic domains. Tensiometry, DLS and viscometry data support the assumption that variations of thermodynamical "favourability" of BAC-BAC or NaHy-BAC interactions take place in hyaluronan solutions, based on the BAC concentration.

• Klíčová slova
• Critical micellar concentration, Dynamic light scattering, Hyaluronan, Hyaluronan conformation, Hyaluronan hydrophobic interactions, Quarternary salts,
• MeSH
• benzalkoniové sloučeniny chemie   MeSH
• konformace sacharidů MeSH
• kyselina hyaluronová chemie   MeSH
• micely MeSH
• povrchové napětí MeSH
• roztoky MeSH
• soli chemie   MeSH
• velikost částic * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzalkoniové sloučeniny MeSH
• kyselina hyaluronová MeSH
• micely MeSH
• roztoky MeSH
• soli MeSH

Conditions facilitating resistance to quaternary ammonium compounds (QACs) were investigated in Staphylococcus aureus SK982 exposed to benzalkonium chloride (BAC; a member of QACs) under various circumstances. S. aureus SK982 carrying the qacA gene encoding for resistance to QACs was grown in the presence of stable or gradually increasing concentrations of BAC, or it was exposed to this antiseptic in the exponential phase of growth. Bacteria cultivated in the highest BAC concentrations that did not retard their growth comparing to the untreated control were subjected to real-time quantitative polymerase chain reaction analysis for relative expression of the efflux genes qacA and norA. Under such conditions, S. aureus SK982 tolerated a relatively low stable concentration of BAC (1.22 mg/L) when compared with a gradually increasing antiseptic concentration (tolerance of 4.88 mg/L). However, in both cases, qacA expression was not significant. The culture exposed in the exponential phase of growth tolerated the highest concentration of BAC (9.76 mg/L) as also accompanied by significant overexpression of qacA. Expression of norA was relatively low regardless of the conditions tested. It seems that under the short-term conditions, the phase of bacterial growth is more important for the expression of BAC resistance than the capability to adapt to this antiseptic. This study provides a deeper insight into the relevance of the qac genes in conferring resistance to QACs.

• MeSH
• antibakteriální látky aplikace a dávkování   farmakologie   MeSH
• bakteriální léková rezistence genetika   MeSH
• bakteriální proteiny genetika   MeSH
• benzalkoniové sloučeniny aplikace a dávkování   farmakologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• membránové transportní proteiny genetika   MeSH
• mikrobiální testy citlivosti MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům genetika   MeSH
• regulace genové exprese u bakterií MeSH
• Staphylococcus aureus účinky léků   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• bakteriální proteiny MeSH
• benzalkoniové sloučeniny MeSH
• membránové transportní proteiny MeSH
• NorA protein, Staphylococcus MeSH Prohlížeč
• proteiny spojené s mnohočetnou rezistencí k lékům MeSH
• qacA protein, Staphylococcus aureus MeSH Prohlížeč

Low-density polyethylene (LDPE) samples were treated in air plasma discharge, coated by polyallyamine brush thought copolymeric grafting surface-from reaction and deposited four common antibacterial agents (benzalkonium chloride, bronopol, chlorhexidine and triclosan) to gain material with active antibacterial properties. Surface characteristics were evaluated by static contact angle measurement with surface energy evaluation ATR-FTIR, X-ray Photoelectron Spectroscopy (XPS) and SEM analysis. Inhibition zone on agar was used as in vitro test of antibacterial properties on two representative gram positive Staphylococcus aureus (S. aureus) and gram negative Escherichia coli (E. coli) strains. It was confirmed, that after grafting of polyallyamine, more antibacterial agent is immobilized on the surface. The highest increase of antibacterial activity was observed by the sample containing triclosan. Samples covered by bronopol did not show significant antibacterial activity.

• MeSH
• allylamin chemie   MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• benzalkoniové sloučeniny chemie   MeSH
• chlorhexidin chemie   MeSH
• fotoelektronová spektroskopie MeSH
• mikrobiální testy citlivosti MeSH
• molekulární struktura MeSH
• polyaminy chemie   MeSH
• polyethylen chemie   MeSH
• propylenglykoly chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• triclosan chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• allylamin MeSH
• antibakteriální látky MeSH
• benzalkoniové sloučeniny MeSH
• bronopol MeSH Prohlížeč
• chlorhexidin MeSH
• polyallylamine MeSH Prohlížeč
• polyaminy MeSH
• polyethylen MeSH
• propylenglykoly MeSH
• triclosan MeSH

Preservatives in eye drops, especially benzalkonium chloride (BAC), may act as cytotoxic; furthermore, it may cause the instability of the tear film, conjunctivitis, subconjunctival fibrosis, epithelium apoptosis and worsening the prognosis of possible surgical treatment. The patient's subjective symptoms may decrease his compliance. For better orientation in this issue, the authors calculated the daily BAC doses in eye drops used in the glaucoma treatment. Significant differences are caused by different size of the drop in specific medicament, different BAC concentrations in the volume unit of the package, and frequency of application. The daily BAC doses are in micrograms as follows: Beta-blockers: Timo-COMOD 0.0, Arutimol 2.6, Vistagan 2.8, Timolol POS 3.0, Arteoptic 3.7, Carteol 4.0, Betoptic S 4.8, Timoptol MSD 6.3, Betoptic 10.0. Alpha-mimetics: Alphagan and Luxfen 3.5, Aruclonine 7.1. Prostaglandin derivates, prostamides and docosanoides: Taflotan 0.0, Lumigan 1.4, Unilat 3.0, Travatan 3.9, Rescula 5.8, Xalatan 6.0, Latanoprost-ratiopharm, Xaloptic, Latanoprost Actavis, Latanoprost Arrow, Solusan, Glaucotens 6.0. Carbonic anhydrase inhibitors: Azopt 4.8, Trusopt 5.4. Fixed combinations: Ganfort 1.4, Combigan 3.2, Duotrav 4.3, Cosopt 5.6, Xalacom 6.0.

• MeSH
• benzalkoniové sloučeniny aplikace a dávkování   analýza   MeSH
• glaukom farmakoterapie   MeSH
• konzervační prostředky farmaceutické aplikace a dávkování   analýza   MeSH
• lidé MeSH
• oční roztoky aplikace a dávkování   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• benzalkoniové sloučeniny MeSH
• konzervační prostředky farmaceutické MeSH
• oční roztoky MeSH

New antifungal agents are needed to treat life-threatening fungal infections, particularly with the development of resistance. Surface-active antifungals have the advantages of minimizing host toxicity and the emergence of drug resistance. We have developed a time-dependent drug exposure assay that allows us to rapidly investigate the mechanism of surface-active antifungal drug action. The assay uses a multidrug pump-deficient strain of Saccharomyces cerevisiae and the potentiometric dye 3,3'-dipropylthiacarbocyanine iodide [diS-C₃(3)] and can assess whether cells are depolarized, hyperpolarized, or permeabilized by drug exposure. In this work, we investigated the mechanisms of action of five surface-active compounds: SDS, nystatin, amphotericin B, octenidine dihydrochloride, and benzalkonium chloride. The diS-C₃(3) time-dependent drug exposure assay can be used to identify the mechanisms of action of a wide range of drugs. It is a fast and cost-effective method for screening drugs to determine their lowest effective concentrations.

• MeSH
• amfotericin B chemie   farmakologie   MeSH
• antifungální látky chemie   farmakologie   MeSH
• benzalkoniové sloučeniny chemie   farmakologie   MeSH
• dodecylsíran sodný chemie   farmakologie   MeSH
• fluorescenční spektrometrie MeSH
• iminy MeSH
• kinetika MeSH
• mikrobiální testy citlivosti metody   MeSH
• nystatin chemie   farmakologie   MeSH
• permeabilita buněčné membrány účinky léků   MeSH
• povrchově aktivní látky chemie   farmakologie   MeSH
• pyridiny chemie   farmakologie   MeSH
• Saccharomyces cerevisiae cytologie   účinky léků   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amfotericin B MeSH
• antifungální látky MeSH
• benzalkoniové sloučeniny MeSH
• dodecylsíran sodný MeSH
• iminy MeSH
• nystatin MeSH
• octenidine MeSH Prohlížeč
• povrchově aktivní látky MeSH
• pyridiny MeSH

Medical-grade polyvinyl chloride was surface modified by a multistep physicochemical approach to improve bacterial adhesion prevention properties. This was fulfilled via surface activation by diffuse coplanar surface barrier discharge plasma followed by radical graft copolymerization of acrylic acid through surface-initiated pathway to render a structured high density brush. Three known antibacterial agents, bronopol, benzalkonium chloride, and chlorhexidine, were then individually coated onto functionalized surface to induce biological properties. Various modern surface probe techniques were employed to explore the effects of the modification steps. In vitro bacterial adhesion and biofilm formation assay was performed. Escherichia coli strain was found to be more susceptible to modifications rather than Staphylococcus aureus as up to 85% reduction in adherence degree of the former was observed upon treating with above antibacterial agents, while only chlorhexidine could retard the adhesion of the latter by 50%. Also, plasma treated and graft copolymerized samples were remarkably effective to diminish the adherence of E. coli.

• MeSH
• antiinfekční látky farmakologie   MeSH
• bakteriální adheze MeSH
• benzalkoniové sloučeniny chemie   MeSH
• biofilmy MeSH
• biokompatibilní materiály chemie   MeSH
• chemické modely MeSH
• chlorhexidin chemie   MeSH
• Escherichia coli metabolismus   MeSH
• polyvinylchlorid chemie   MeSH
• povrchové vlastnosti MeSH
• propylenglykoly chemie   MeSH
• racionální návrh léčiv MeSH
• smáčivost MeSH
• Staphylococcus aureus metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiinfekční látky MeSH
• benzalkoniové sloučeniny MeSH
• biokompatibilní materiály MeSH
• bronopol MeSH Prohlížeč
• chlorhexidin MeSH
• polyvinylchlorid MeSH
• propylenglykoly MeSH