Generic selection criteria for safety and patient benefit [â «]: Comparing the physicochemical and pharmaceutical properties of brand-name and generic tulobuterol tape.

Physicochemical properties (drug release, peel strength, adhesion, and stiffness) of Hokunalin® Tape (Hokunalin) and 13 generic transdermal bronchodilator patches containing tulobuterol were characterized and evaluated for comparison. Drug-release studies evaluating sustained release behavior demonstrated better performance by the drug Hokunalin, than the generics MED, YP, Sawai, and Teikoku. Hokunalin yield a 16.2% release 1 hour after initiation, 30.1% at 3 hours, 50.0% at 8 hours. In comparison, the generics MED, YP, Sawai, and Teikoku showed an intermediate release behavior to that of Hokunalin, with more than 80% release after 8 hours. A 90-degree peel adhesion test for tape peel strength demonstrated that the generic MED (4.99 N), YP (3.26 N), Sawai (4.17 N), and Teikoku (4.37 N) tapes yielded significantly higher values compared to Hokunalin (2.66 N). Probe tack tests, evaluating adhesive strength, yielded significantly higher values for the generics HMT (4.89 N)and Towa (4.25 N) compared to Hokunalin (3.66 N). Furthermore, for the stiffness-softness test, a significantly higher value was obtained for each generic yielded compared to Hokunalin (3.7-degree). These factors are important components of product qualities that affect treatment efficacy, including "ease of application" and other usability factors.

Single intratracheal administration toxicity study on safety of vapor inhalation of electrolyzed reduced water in rats.

The effects of acute intratracheal administration of electrolyzed reduced water (ERW; alkaline electrolyzed water) were investigated in rats. In this study, no deaths or near-deaths were recorded in either group, namely those treated with ERW or purified water (maximum doses of 900 mg/kg). The main symptoms observed in the rats were decreased spontaneous movements and abnormal breath sounds, which were considered to be transient symptoms caused by intratracheal administration. In addition, low values of alkaline phosphatase, total protein and lactate dehydrogenase were found in BALF tests, but these values were considered to be of low toxicological significance, since they are usually high in the presence of lung inflammation or cellular damage. This suggests that the alkalinity of ERW partially contributes to broken peptide bonds in proteins. There were no significant increases in bronchoalveolar lavage fluid protein in either group. ERW did not cause an increase in the influx of neutrophils, eosinophils, basophils, or lymphocytes, suggesting that intratracheal administration of ERW did not cause lung inflammation. ERW did not cause abnormalities in the body or pathological changes in the lungs. Aggregates of alveolar macrophages, as a measure of inflammation, were observed in both groups. These may be transient symptoms due to intratracheal administration, not due to ERW toxicity. This study confirmed the safety of intratracheal ERW infusion and demonstrated the low risk of acute toxicity for inhalation exposure to ERW aerosol or vapor. Therefore, ERW may be an effective air purifier against viruses or bacteria.

Generic selection criteria for safety and patient benefit [XI]: Usability scores of brand-name and generic tapes containing sodium diclofenac by questionnaire survey.

The aim of this study was to evaluate patient satisfaction and usability scores of different tape treatments and examine the scores in relation to the mechanical characteristics of the tape formulation. A questionnaire for the assessment of comfort level and satisfaction with two brand-name (Naboal, Voltaren) and four generic tapes (Yutoku, Teikoku, Rakool, Towa) containing sodium diclofenac was developed and then applied to 12 healthy volunteers. Results showed that Voltaren was difficult to apply to the skin and easier to peel off the skin than Naboal (p < 0.01). Moreover, Rakool was easier to peel than Naboal (p < 0.05). The mechanically measured peeling force was associated with pain during peeling off (r = -0.65), and the measured value of bending rigidity was associated with ease of peeling off (r = -0.97). The knowledge obtained regarding the influence of pharmaceutical properties on the degree of satisfaction with and usability of different tape formulations may be useful for supporting the selection of generic tapes tailored to individual needs or pharmacist preferences, and thus improve treatment adherence and clinical outcomes.

Physicochemical properties and detergency of special electrolytic-reduction ion water.

The detergency of special electrolytic-reduction ion water (S-100) was evaluated in comparison with typical synthetic surfactants. Furthermore, to examine the cleaning mechanism of S-100, various physicochemical characteristics of S-100 were measured and a comprehensive evaluation of cleaning was performed. S-100 (10%) had a detergency comparable to that of various surfactants, such as sodium dodecyl sulfate and sodium dodecyl benzene sulfonate, which are generally blended or mixed in residential detergents. In addition, concentrated aqueous solutions of 10% or more of S-100 showed stronger detergency. The cleaning mechanism of S-100 is mainly attributed to the effect of surface tension reduction due to dissolved hydrogen or hydrogen nanobubbles in S-100, and the alkalinity generated by electrolysis charged the surface of the dirt or adherend, resulting in a peeling effect.

Antiviral effect of electrolyzed reduced water on SARS-CoV-2.

The inhibitory activity of electrolyzed reduced water (ERW) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is the etiological agent responsible for coronavirus disease 2019 (COVID-19), was tested in vitro on Vero E6 cells using a plaque assay. Infectious virus titers of cells treated with ERW 100%, 50% and 33.3% solutions and phosphate buffered saline (PBS, negative control) and exposed to the virus suspension for 60 seconds were 2.25, 2.65, 3.21 and 7.38, respectively. ERW has a high pH and low surface tension. It is considered that the alkaline property of ERW breaks down phospholipids and proteins of envelopes. The role of pH and reducibility on the virucidal effect of ERW should be further evaluated. This study provides a foundation for utilizing ERW as an effective antiviral aqueous solution in a variety of applications.

Generic selection criteria for safety and patient benefit [X]: Water-vapor permeability and peel force properties of brand-name and generic ketoprofen tapes.

Tape products containing ketoprofen have transdermal analgesic and anti-inflammatory effects. We compared the physicochemical properties (water-vapor permeability, peel force, peel force-time curve) between one brand-name product and eight generic products. Regarding the measurement of water-vapor permeability, the formulations using methacrylic acid n-butyl acrylate copolymer (MBA) adhesives showed higher water-vapor permeability than those using styrene isopropyl styrene block copolymer (SIS) adhesives. In the case of the formulation using SIS adhesive, the central part of the formulation had higher water-vapor permeability than both ends. In the 90-degree peel test using the methods of adhesion testing, significant differences were observed between the products, especially as the various application times (5 min, 30 min, 9 h and 24 h) increased. This may be because the longer the time of attachment to the adherend, the more the adhesive force with the adherend increased due to the "anchoring effect" of the adhesive. The measurement of the peel force-time curve showed different curves among the products, especially in the peel force curve of Teikoku after 24 h, which showed two characteristic peak curves. Furthermore, when the peel forces at 25°C and 40°C were compared, Mohrus and Toko showed significantly higher values at 40°C compared to 25°C. This study showed that there are many generic drugs with formulation characteristics different from those of brand-name drugs, and that there is a large difference among the products in terms of adhesion and detachment.

Anesthetic Potency of Intravenous Infusion of 20% Emulsified Sevoflurane and Effect on the Blood-Gas Partition Coefficient in Dogs.

BACKGROUND: Intravenous (IV) infusions of volatile anesthetics in lipid emulsion may increase blood lipid concentration, potentially altering the anesthetic agent's blood solubility and blood-gas partition coefficient (BGPC). We examined the influence of a low-lipid concentration 20% sevoflurane emulsion on BGPC, and the anesthetic potency of this emulsion using dogs. METHODS: We compared BGPC and anesthetic characteristics in 6 dogs between the IV anesthesia of emulsion and the sevoflurane inhalation anesthesia in a randomized crossover substudy. Minimum alveolar concentrations (MACs) were determined by tail-clamp stimulation by using the up-and-down method. Blood sevoflurane concentration and partial pressure were measured by gas chromatography; end-tidal sevoflurane concentration was measured using a gas monitor. The primary outcome was BGPC at the end of IV anesthesia and inhalation anesthesia. Secondary outcomes were time to loss/recovery of palpebral reflex, finish intubation and awakening, MAC, blood concentration/partial pressure at MAC and awakening, correlation between blood partial pressure and gas monitor, and the safety of emulsions. RESULTS: BGPC showed no difference between IV and inhaled anesthesia (0.859 [0.850-0.887] vs 0.813 [0.791-0.901]; P = .313). Induction and emergence from anesthesia were more rapid in IV anesthesia of emulsion than inhalation anesthesia. MAC of emulsion (1.33% [1.11-1.45]) was lower than that of inhalation (2.40% [2.33-2.48]; P = .031), although there was no significant difference in blood concentration. End-tidal sevoflurane concentration could be estimated using gas monitor during IV anesthesia of emulsion. No major complications were observed. CONCLUSIONS: IV anesthesia with emulsion did not increase the BGCP significantly compared to inhalation anesthesia. It was suggested that the anesthetic potency of this emulsion may be equal to or more than that of inhalation.

Generic selection criteria for safety and patient benefit [IX]: Evaluation of "feeling of use" of sodium hyaluronate eye drops using the Haptic Skill Logger (HapLog®) wearable sensor for evaluating haptic behaviors.

We compared the pharmaceutical properties, such as surface tension, drop volume, nozzle inner diameter, and force to push the drug product out of the container (squeeze force), of purified sodium hyaluronate eye drops preparations of one brand-name (Hyalein) and 11 generic drugs used for treatment of keratoconjunctiva epithelial disorders, and examined product selection based on the needs of the patient. The surface tension of Nissin (51.0 dyn/cm) and Nitten (52.3 dyn/cm) was significantly lower than that of Hyalein (62.8 dyn/cm), whereas Nitten PF (69.5 dyn/cm) was significantly higher than Hyalein. The drop volume of Tearbalance (42.4 mg), Nissin (43.7 mg), and Nitten (42.7 mg) was significantly lower than that of Hyalein (50.4 mg). We compared the squeeze force using a wearable touch sensor (Haptic Skill Logger: HapLog®) and digital force gauge (DF). The squeeze force of HapLog® showed values of about 1.7- to 3.5-fold higher than that of DF. Moreover, the squeeze force of Eyecare (34.0 N), Kyorin (35.4 N), and Nitten PF (44.3 N) by HapLog® was significantly higher than that of Hyalein (10.5 N). In contrast, the squeeze force of Kyorin (20.8 N) and Nitten PF (25.0 N) by DF was significantly higher than that of Hyalein (12.2 N). Two questionnaire surveys on the feeling of instillation of eye drops revealed a strong negative correlation between feeling of use and squeeze force.

Generic selection criteria for safety and patient benefit [VIII]: Comparing the physicochemical and pharmaceutical properties of brand-name and generic diclofenac sodium tapes.

With respect to diclofenac sodium-containing tape preparations of nonsteroidal antiphlogistic drug, we compared the pharmaceutical properties (pH, elongatedness, water-vapor permeability, adhesive force, and peeling-force) of 11 medicinal drugs (2 brand-name and 9 generic drugs) to obtain evidence for product selection in line with the needs of the patient. The elongatedness of the generic drugs Teikoku (1.39), Yutoku (1.40), and Nippon-zoki (1.43) were significantly higher than the brand-name drug Voltaren® (1.22). The adhesive force was measured using the probe tack test and the inclined ball tack test. The probe tack test results of Naboal® (6.8 N/cm2), Teikoku (6.1 N/cm2), Yutoku (5.9 N/cm2), Nippon-zoki (6.2 N/cm2), and Rakool (6.2 N/cm2) were higher than that of Voltaren (2.0 N/cm2). The inclined ball tack test results of Naboal (18.0), Teikoku (24.0), Yutoku (21.5), and Nippon-zoki (22.7) were also higher than that of Voltaren (7.2). Concerning peeling-force measurement, the 90° peeling-forces of Naboal (0.95 N), Teikoku (0.96 N), Yutoku (0.94 N), and Nippon-zoki (1.01 N) were higher than that of Voltaren (0.68 N). These results show that there were marked differences in the feeling of use of each product between the brand-name and generic drugs. The pharmacist indicates the basis for selection of a preparation according to the feeling of use desired by each patient. It has become possible to recommend products suitable for each patient, which will allow pharmacists to provide products according to the needs of each patient when a brand-name drug is changed to a generic one.

Criteria for the selection of switch OTC drugs based on patient benefits, efficacy, and safety [II]: Comparing the physicochemical and pharmaceutical properties of brand-name and switch OTC terbinafine hydrochloride cream.

The physicochemical properties (pH, yield value, and squeeze force) of a drug for dermatomycosis, a terbinafine hydrochloride-containing cream (a brand-name product), and 12 over-the-counter drugs (OTCs) were measured and compared to ascertain the characteristics of each product. The pH of the brand-name product, Lamisil, was 4.1, and that of the OTC products ranged from 4.2 to 7.6; Lamisil Plus (7.6) had a significantly higher pH. Moreover, the yield value for Lamisil, as an index of cream ductility, was 128 dyn/cm2, and that for the OTC products ranged from 110 to 887 dyn/cm2. In particular, the OTC products Damalin (887 dyn/cm2), Barriact (512 dyn/cm2), and Exiv Deep (663 dyn/cm2) had a significantly higher yield value. In addition, the squeeze force was measured by attaching a HapLog® to the thumb and second finger. The squeeze force for Lamisil was 12.9 N, and that for the OTC products ranged from 1.8 to 14.6 N. The OTC product Bilumon (1.8 N) had a significantly lower squeeze force. These results indicated that there were marked differences in the pharmaceutical properties of brand-name and OTC products. External preparations are characterized by their feel during use. Based on the current results, the pharmaceutical characteristics of drugs resulted in differences in their feel during use, suggesting that products appropriate for individual patients can be recommended.

Generic selection criteria for safety and patient benefit [VII]: Comparing the physicochemical and pharmaceutical properties of brand-name and generic terbinafine hydrochloride cream.

We measured and compared the physicochemical properties (pH, yield value, and squeeze force) of a drug for dermatomycosis, terbinafine hydrochloride-containing cream (brand-name product), and 12 generic products to clarify the characteristics of each product. On pH measurement, the pH value of the brand-name product, Lamisil, was 4.8, and those of the generic products ranged from 4.3 to 5.5, showing no marked difference. Furthermore, the yield value of Lamisil, as an index of cream ductility, was 122.2 dyn/cm2, and those of the generic products ranged from 42.1 to 1,621.5 dyn/cm2. In particular, the value of a generic product, Taiyo (42.1 dyn/cm2), was significantly lower, whereas that of another one, Viras (1,621.0 dyn/cm2), was significantly higher. In addition, the squeeze force was measured by attaching a HapLog® to the thumb and second finger. The value of Lamisil was 12.9 N, and those of the generic products ranged from 8.0 to 15.4 N. The values of generic products, Mylan (8.6 N), Tebinaceil (9.0 N), and Kelger (8.0 N), were significantly lower, whereas that of another one, Viras (15.4 N), was significantly higher. These results showed that there were marked differences in the pharmaceutical properties between the generic and brand-name products. The above pharmaceutical characteristics of drugs facilitated the presentation of reasons for differences in the sense of use, which characterizes external preparations, suggesting that products appropriate for individual patients can be recommended.

Ability of community pharmacists to promote self-care and self-medication by local residents [I]: Improvements in bone mineral density.

This study was conducted in order to establish a health management method for the elderly in a community through follow-ups of bone mineral density (BMD) measurement results over a 1-year period based on BMD measurements performed by pharmacists and a guidance program. Regarding BMD measurement results, the percent young adult mean (%YAM: mean BMD in healthy persons of the same sex aged between 51 and 82 years old) significantly increased in Period I, during which the intervention by pharmacists was performed (6 months after the start of measurements), but significantly decreased in Period II, during which this intervention was not performed (between 7 and 12 months after the start of measurements). Based on these results, lifestyle improvements were effective in Period I regardless of sex or age; however, it may be important to maintain an improved diet and subject motivation in the future. The results of this study suggest that community pharmacists play an important role in community medicine through positive intervention for local residents' health support.

Generic selection criteria for safety and patient benefit [VI]: Comparing the physicochemical and pharmaceutical properties of brand-name, generic, and OTC felbinac tapes.

We measured the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time of medicinal and over-the-counter (OTC) tape preparations containing felbinac. When measuring the pH of each preparation, Felnabion (pH 4.5) was weakly acidic, and EMEC and Tokuon (pH 7.0) were neutral. When measuring the water-vapor permeability of each preparation, that of a generic product, EMEC (380 g/m2/24h), was twice as high as that of a brand-name product, Seltouch (189 g/m2/24 h). The adhesive force was measured using the ball tack test. The adhesive forces of OTC drugs, Salomethyl, Homepass, and Tokuhon (1.04 g), were higher than that of Seltouch (0.06 g). Concerning peeling-force measurement, the peeling-forces of a generic product, Falzy (4.15 N), and an OTC drug, Omuneed (4.89 N), were higher than that of Seltouch (0.91 N). The elongation rates of a generic product, Sumilu (319%), and OTC drugs, Nabolin (298%) and Homepass (299%), were higher than that of Seltouch (251%), but that of Tokuhon (72%) was lower. The support flexibilities of EMEC (150 degrees) and Tokuhon (131 degrees) were higher than that of Seltouch (96 degrees). In addition, the peeling time of Seltouch was 120 min or more, whereas those of EMEC and Nabolin were 1.4 and 0.2 min, respectively. These results suggest that the differences in pharmaceutical properties, such as the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time, among the preparations markedly influence patients' subjective comfortableness. The results of this study facilitated individuals' comfortableness-matched drug selection.

Generic selection criteria for safety and patient benefit [V]: Comparing the pharmaceutical properties and patient usability of original and generic nasal spray containing ketotifen fumarate.

The pH, osmotic pressure (cryoscopy), viscosity, squeeze force, spray angle, and spraying frequency of nasal spray containing ketotifen fumarate (1 brand-name product and 8 generic products) were measured. Based on the results of pH measurement, all products were weakly acidic (4.0 to 5.1). For all products, the osmotic pressure ratio to physiological saline was approximately 1. The viscosity of various products ranged from approximately 1.0 to 1.5 mPa·s. The spray angle of drug solution differed among the products: minimum, 46 degrees (Sawai and Fusachol); and maximum, 68.7 degrees (Sekiton). In particular, TOA, Sawai, Fusachol, and TYK showed significantly smaller angles compared to Zaditen (brand-name product). Container properties varied among the products: minimum squeeze force, 19.0 N (Sekiton); and maximum squeeze force, 43.1 N (Sawai). Based on these results, although all the above products are identical in dosage form and active ingredient, the differences in pharmaceutical properties, such as container operations and drug-solution spraying/attachment, may markedly influence patients' subjective opinions.

The Effectiveness and Stability of a 20% Emulsified Sevoflurane Formulation for Intravenous Use in Rats.

BACKGROUND: Halogenated volatile anesthetics can be safely and rapidly administered to animals and humans using emulsion formulations. However, they must be administered simultaneously with a high dose of lipids. Increasing the concentration of volatile anesthetics may solve this clinical issue. Moreover, careful observation is needed when the emulsion is injected because anaphylactic reactions have been reported. METHODS: We prepared a 20% sevoflurane lipid emulsion and administered it to 69 male Sprague-Dawley rats via the tail vein. The median effective dose (ED50) for the loss of righting reflex and the median lethal dose (LD50) were determined. ED50 and LD50 values were calculated using nonlinear regression, and data were fitted with a cumulative Gaussian model using GraphPad Prism. Measurements of vital signs and evaluation of the presence of adverse effects associated with continuous infusion of emulsions were verified. Stability of the emulsion was assessed by measuring particle size at 365 days and sevoflurane concentrations after opening the vial at 180 minutes. RESULTS: The ED50 and LD50 were 0.47 mL/kg (95% confidence interval [CI], 0.46-0.48) and 1.13 mL/kg (95% CI, 1.07-1.18), respectively. The therapeutic index (LD50/ED50) was 2.41 (95 CI%, 2.23-2.59), which compares favorably with therapeutic index of a fluoropolymer-based emulsion of sevoflurane, propofol, and thiopental. There were no adverse effects associated with the continuous infusion of emulsions. Particle size of the emulsion at 365 days after preparation was 78.9 ± 3.8 nm (±SD), and sevoflurane concentration at 180 minutes after opening the vial was 19.0% ± 0.6% (±SD). CONCLUSIONS: We prepared a 20% sevoflurane lipid emulsion using caprylic triglyceride (i.e., medium-chain triglyceride). In rats, this emulsion was an effective anesthetic and was not associated with adverse events. The emulsion was stable after consecutive evaluation for 365 days and for 180 minutes after the vial was opened.

Generic Selection Criteria for Safety and Patient Benefit [IV] - Physicochemical and pharmaceutical properties of brand-name and generic ketoprofen tapes.

The physicochemical and pharmaceutical properties (pH, peel force, water-vapor permeability, and stretchability) of brand-name and generic ketoprofen products were evaluated and compared. The pHs of Mohrus as a brand-name product and Teikoku as a generic product were low (about 4). Among the other generic products, Patell and Nichi-Iko had a pH of about 4.3 while Frestol, Raynanon, BMD, and Touchron showed a pH of 4.6-5.2, which was in the pH range of normal healthy skin (4.5-6.5). The adhesive force was high (≥ 1.38) for Mohrus as a brand-name product as well as for Teikoku and Patell as generic products, but it was low (≤ 0.57) for the other 5 generic products. The water-vapor permeabilities of Mohrus as a brand-name product and Teikoku and Patell as generic products were low, being less than 1/6 of those for the other 5 generic products. Among the 5 generic products, BMD showed the highest water-vapor permeability (1,330 g/m²), and the other products also showed a value ≥ 1,100 g/m². The elongatedness of Mohrus was the lowest (15.5 cm), and that of Raynanon was the highest (24.5 cm); the difference was 9 cm. In this study, the physiochemical and pharmaceutical properties of ketoprofen tapes were clarified, which will allow pharmacists to provide products according to the needs of each patient when a brand-name product is changed to a generic one.

Preparation and physicochemical properties of surfactant-free emulsions using electrolytic-reduction ion water containing lithium magnesium sodium silicate.

Surfactant-free emulsions by adding jojoba oil, squalane, olive oil, or glyceryl trioctanoate (medium chain fatty acid triglycerides, MCT) to electrolytic-reduction ion water containing lithium magnesium sodium silicate (GE-100) were prepared, and their physiochemical properties (thixotropy, zeta potential, and mean particle diameter) were evaluated. At an oil concentration of 10%, the zeta potential was ‒22.3 ‒ ‒26.8 mV, showing no marked differences among the emulsions of various types of oil, but the mean particle diameters in the olive oil emulsion (327 nm) and MCT emulsion (295 nm) were smaller than those in the other oil emulsions (452-471 nm). In addition, measurement of the hysteresis loop area of each type of emulsion revealed extremely high thixotropy of the emulsion containing MCT at a low concentration and the olive emulsion. Based on these results, since surfactants and antiseptic agents markedly damage sensitive skin tissue such as that with atopic dermatitis, surfactant- and antiseptic-free emulsions are expected to be new bases for drugs for external use.

Physicochemical properties and controlled drug release of microcapsules prepared by simple coacervation.

Ternary phase diagrams of gelatin-water-methanol, gelatin-water-ethanol, and gelatin-water-propanol systems were prepared to evaluate optimal coacervation. The results of their evaluation suggested that the optimal coacervation region expands with the hydrophobicity of the added poor solvent (methanol, ethanol, 1-propanol, and 2-propanol). Microcapsules prepared based on the optimal coacervation region differed in controlled drug release among poor solvents used even when the concentration of gelatin, a membrane component, is the same. Compared with microcapsules prepared using the gelatin-water-ethanol system, those prepared using the gelatin-water-propanol system showed a 34% decrease in the drug release rate 24h after the initiation of the drug release test. These results suggested that microcapsules prepared using gelatin-water-various lower alcohol systems can readily control drug release and can be a useful drug delivery system (DDS).

Adsorption of various antimicrobial agents to endotoxin removal polymyxin-B immobilized fiber (Toraymyxin®). Part 2: Adsorption of two drugs to Toraymyxin PMX-20R cartridges.

In our previous study, the degree of adsorption of 9 representative antimicrobial agents to Toraymyxin(®) PMX-F sheets was quantitatively evaluated. As a result, the adsorption rate was 22.1% for Linezolid in the presence of serum. Therefore, we investigated whether two types of antimicrobial agents (Ciprofroxacin and Linezolid) can be better adsorbed on PMX-F sheets. When the number of PMX-F sheets was increased in a step wise manner, specifically 2, 4, 6, 8 and 12, the adsorption rate increased linearly. In addition, the adsorption to polymyxin-B immobilized fiber (Toraymyxin(®) PMX-20R) cartridges, widely used to remove endotoxins from circulating blood in the treatment of sepsis, was quantitatively evaluated. As a result, in the presence of serum, Linezolid showed adsorption to PMX-20R, and the adsorption rate after 2h was 54.5%, and that after 4h was 65.8%. The results of this study suggest the necessity of monitoring blood antimicrobial concentration during treatment for sepsis with Linezolid, which showed adsorption to PMX-20R in an environment close to a clinical environment.

Adsorption of various antimicrobial agents to endotoxin removal polymyxin-B immobilized fiber (Toraymyxin®).

The presence/absence of adsorption of 9 representative types of antimicrobial agent used in combination with a polymyxin-B immobilized fiber (PMX-F) were determined and the degree of adsorption to PMX-F was quantitatively evaluated. Various antimicrobial agents were dissolved at appropriate concentrations, and PMX-F was added to each solution and incubated at 37°C. Antimicrobial solutions without PMX-F were also similarly incubated as controls. After 2 and 4h, the concentration of each antimicrobial agent was determined using HPLC. To produce an environment closer to the in vivo state, albumin or serum was added, and similar evaluation was performed. In the presence of albumin, the rate of adsorption to PMX-F was relatively high for Cefmetazon(®), Pentcillin(®), Ciproxan(®) and Zyvox(®). In the presence of serum, the adsorption rate was 4.02±2.83% for Pentcillin(®), 5.59±1.00% for Ciproxan(®), and 22.12±3.23% for Zyvox(®). The results of this study suggest that adequate caution is necessary on the clinical use of Zyvox(®), which was adsorbed in the presence of serum as an environment close to the in vivo environment, but the use of other antimicrobial agents in combination with PMX-F may have only slight influences on adsorption to PMX-F.