Simulated Y-site compatibility of atosiban acetate with selected intravenous drugs.

OBJECTIVE: The physical compatibility of atosiban and selected drugs during simulated Y-site administration was evaluated. We also searched for any compatibility predictions regarding its physicochemical properties. STUDY DESIGN: Test admixtures were prepared by mixing 5 mL of each study drug solution with 5 mL of atosiban solution in a 1:1 ratio to simulate Y-site infusion. Assessments were made immediately after mixing (baseline), and at 0.5, 1, and 3 h. Visual incompatibility was defined as a presence of haze or any visible particulate matter, gas formation, or colour change. Turbidity and pH variation of the admixtures were also assessed using instrumental methods. RESULTS: None of the admixtures used with atosiban exhibited visual changes and no incompatibility regarding instrumental methods were observed, because no admixture had an increase of 0.5 nephelometric turbidity units, and no pH change was above one unit when compared to baseline. However, the pH of ampicillin and omeprazole admixtures fell outside of the atosiban stability range. CONCLUSIONS: Our study showed no physical incompatibility between atosiban and the test drugs in terms of visual changes or nephelometric and pH measurements. However, we recommend against atosiban and ampicillin or omeprazole coadministration until complementary compatibility studies are performed.

Swine as the Animal Model for Testing New Formulations of Anti-Inflammatory Drugs: Carprofen Pharmacokinetics and Bioavailability of the Intramuscular Route.

Carprofen (CP) is a non-steroidal anti-inflammatory drug (NSAID) frequently used to treat respiratory diseases in numerous small animals, but also in large species. CP is a formidable candidate for further therapeutic research of human inflammatory diseases using the pig as an animal model. However, CP administration in swine is very uncommon and respective pharmacokinetics/bioavailability studies are scarce. A simultaneous population pharmacokinetic analysis after CP intravenous and intramuscular administrations in pigs has shown high extent and rate of absorption and a similar distribution profile with respect to man and other mammals. However, clearance and half-life values found in swine suggest a slower elimination process than that observed in man and some other animal species. Although not reported in other species, liver and kidney concentrations achieved at 48 h post-intramuscular administration in pigs were ten times lower than those found in plasma. Simulations pointed to 4 mg/kg every 24 h as the best dosage regimen to achieve similar therapeutic levels to those observed in other animal species. All these findings support the use of pig as an animal model to study the anti-inflammatory effects of CP in humans.

Comisión de terapias biológicas. ¿Qué nos aporta? / Biologic therapies committee. What does it provide?

OBJETIVO: Evaluar el impacto general a nivel asistencial de una comisión de terapias biológicas, en enfermedades inflamatorias inmunomediadas, mediante los hábitos de prescripción, los estudios prebiológicos y la inmunización. MÉTODO: Se realizó un estudio cuasiexperimental sobre todos los pacientes naïve mayores de edad que iniciaron tratamiento con un medicamento biológico por enfermedad inflamatoria inmunomediada el año anterior y el año posterior a la creación de la comisión de terapias biológicas. RESULTADOS: Se incluyeron un total de 31 pacientes estudiados en 2016 y 40 pacientes estudiados en 2018. La prescripción de medicamentos inhibidores del factor de necrosis tumoral α se redujo en 2018 (80,6% versus 45,0%; p < 0,05), mientras que la prescripción de inhibidores de la interleucina 12/23 aumentó (12,9% versus 35,0%; p < 0,05). El cribaje tuberculoso fue estadísticamente diferente entre los periodos pre y postcomisión de terapias biológicas: la realización del interferon gamma release assay fue superior en 2018 (9,7% versus 80,0%, p < 0,01) y la proporción de pacientes que realizaron correctamente la quimioprofilaxis fue superior en 2018 (36,4% versus 81,8 % , p < 0,05). La proporción de pruebas solicitadas para estudio de patologías víricas, así como la administración de vacunas, fueron superiores en 2018. CONCLUSIONES: El desarrollo de una comisión específica de terapias biológicas aporta mejoras asistenciales en enfermedades inflamatorias inmunomediadas, al contribuir a un mayor conocimiento relacionado con los medicamentos y con la prevención de los efectos adversos de carácter infeccioso, por lo que sería conveniente que se impulsara el desarrollo de comisiones especializadas como la comisión de terapias biológicas

OBJECTIVE: To assess the general healthcare impact of a Biological Therapies Commitee (immune-mediated inflammatory diseases) through prescription habits, pre-biological studies and immunization. METHOD: A quasi-experimental study was conducted on all naïve patients of legal age who started treatment with a biological agent for an immune-mediated inflammatory disease the year before and the year after the creation of the Biological Therapies Committee. RESULTS: A total of 31 patients treated in 2016 and 40 patients treated in 2018 were included. Prescriptions of tumor necrosis factor alpha inhibitor drugs decreased in 2018 (from 80.6% to 45.0%, p < 0.05), while prescriptions of interleukin 12/23 inhibitors increased (from 12.9% to 35.0%, p < 0.05). Tuberculosis screening was statistically different between the two periods: the number of interferon gamma release assays performed was higher in 2018 (from 9.7% to 80.0%, p < 0.01) and the proportion of patients who successfully underwent chemoprophylaxis was higher in 2018 (from 36.4% to 81.8%, p < 0.05). The proportion of tests requested for the study of viral pathologies and the number of vaccines administered were also higher in 2018. CONCLUSIONS: The development of a specific Biological Therapies Committee allows healthcare improvements, contributing to a deeper understanding of the medications and to preventing the infection-related adverse events. It would therefore seem advisable to develop specialized committees akin to the Biological Therapies Committee in other domains

Topical Amphotericin B Semisolid Dosage Form for Cutaneous Leishmaniasis: Physicochemical Characterization, Ex Vivo Skin Permeation and Biological Activity.

Amphotericin B (AmB) is a potent antifungal successfully used intravenously to treat visceral leishmaniasis but depending on the Leishmania infecting species, it is not always recommended against cutaneous leishmaniasis (CL). To address the need for alternative topical treatments of CL, the aim of this study was to elaborate and characterize an AmB gel. The physicochemical properties, stability, rheology and in vivo tolerance were assayed. Release and permeation studies were performed on nylon membranes and human skin, respectively. Toxicity was evaluated in macrophage and keratinocyte cell lines, and the activity against promastigotes and intracellular amastigotes of Leishmania infantum was studied. The AmB gel remained stable for a period of two months, with optimal properties for topical use and no apparent toxic effect on the cell lines. High amounts of AmB were found in damaged and non-damaged skin (1230.10 ± 331.52 and 2484.57 ± 439.12 µg/g/cm2, respectively) and they were above the IC50 of AmB for amastigotes. Although there were no differences in the in vitro anti-leishmanial activity between the AmB solution and gel, the formulation resulted in a higher amount of AmB being retained in the skin, and is therefore a candidate for further studies of in vivo efficacy.

Biologic therapies committee. What does it provide?

OBJECTIVE: To assess the general healthcare impact of a Biological  Therapies Commitee (immune-mediated inflammatory diseases) through  prescription habits, pre-biological studies and immunization. METHOD: A quasi-experimental study was conducted on all naïve patients  of legal age who started treatment with a biological agent for an immune- mediated inflammatory disease the year before and the year after the  creation of the Biological Therapies Committee. RESULTS: A total of 31 patients treated in 2016 and 40 patients treated in 2018 were included. Prescriptions of tumor necrosis factor alpha  inhibitor drugs decreased in 2018 (from 80.6% to 45.0%, p < 0.05), while prescriptions of interleukin 12/23 inhibitors increased (from 12.9% to  35.0%, p < 0.05). Tuberculosis screening was statistically different  between the two periods: the number of interferon gamma release assays  performed was higher in 2018 (from 9.7% to 80.0%, p < 0.01) and the  proportion of patients who successfully underwent chemoprophylaxis was  higher in 2018 (from 36.4% to 81.8%, p < 0.05). The proportion of tests  requested for the study of viral pathologies and the number of vaccines  administered were also higher in 2018. CONCLUSIONS: The development of a specific Biological Therapies  Committee allows healthcare improvements, contributing to a deeper  understanding of the medications and to preventing the infection-related  adverse events. It would therefore seem advisable to develop specialized  committees akin to the Biological Therapies Committee in other domains.

Objetivo: Evaluar el impacto general a nivel asistencial de una comisión  de terapias biológicas, en enfermedades inflamatorias inmunomediadas,  mediante los hábitos de prescripción, los estudios prebiológicos y la  inmunización.Método: Se realizó un estudio cuasiexperimental sobre todos los  pacientes naïve mayores de edad que iniciaron tratamiento con un  medicamento biológico por enfermedad inflamatoria inmunomediada el  año anterior y el año posterior a la creación de la comisión de terapias  biológicas.Resultados: Se incluyeron un total de 31 pacientes estudiados en 2016 y  40 pacientes estudiados en 2018. La prescripción de medicamentos inhibidores del factor de necrosis tumoral α se redujo en  2018 (80,6% versus 45,0%; p < 0,05), mientras que la prescripción de  inhibidores de la interleucina 12/23 aumentó (12,9% versus 35,0%; p <  0,05). El cribaje tuberculoso fue estadísticamente diferente entre los  periodos pre y postcomisión de terapias biológicas: la realización del  interferon gamma release assay fue superior en 2018 (9,7% versus  80,0%, p < 0,01) y la proporción de pacientes que realizaron  correctamente la quimioprofilaxis fue superior en 2018 (36,4% versus  81,8%, p < 0,05). La proporción de pruebas solicitadas para estudio de  patologías víricas, así como la administración de vacunas, fueron  superiores en 2018.Conclusiones: El desarrollo de una comisión específica de terapias biológicas aporta mejoras asistenciales en enfermedades  inflamatorias inmunomediadas, al contribuir a un mayor conocimiento  relacionado con los medicamentos y con la prevención de los efectos  adversos de carácter infeccioso, por lo que sería conveniente que se  impulsara el desarrollo de comisiones especializadas como la comisión de  terapias biológicas.

In Vivo Anti-inflammatory and Antiallergic Activity of Pure Naringenin, Naringenin Chalcone, and Quercetin in Mice.

Flavonoids, found in almost all fruits and vegetables, belong to a class of plant secondary metabolites with a polyphenolic structure and have properties with health-improving potential. However, few experimental studies on the effects of flavonoids have been carried out in vivo after external application and using pure compounds. Aiming to fill this gap, in this study we tested the topical anti-inflammatory and antiallergic activity of three flavonoids of high purity, naringenin, naringenin chalcone, and quercetin, in mouse models. The topical anti-inflammatory effects were assessed against arachidonic acid- (AA) and tetradecanoylphorbol-13-acetate- (TPA) induced ear edema. The anti-inflammatory effect of naringenin against ear edema was noticeable at a 1% dose in the AA model and at half this dose in the TPA model. Quercetin (1.3%) did not exert any topical anti-inflammatory activity in the AA model, but its inhibitory effect in the TPA model was similar to that of naringenin (2%); in contrast, naringenin chalcone was more active against the AA-induced than TPA-induced inflammation. The flavonoid effect on IgE-mediated passive cutaneous anaphylaxis was also studied in mice, both intravenously and topically. Naringenin, naringenin chalcone, and quercetin all showed strong antiallergic activity after intravenous dosing (0.02%) and when applied topically (2%). The results of this study suggest that the flavonoids naringenin, naringenin chalcone, and quercetin may be useful alternatives for the topical treatment of inflammatory and allergic skin disorders.

Direct estimation of the permeation of topical excipients through artificial membranes and human skin with non-invasive Terahertz time-domain techniques.

BACKGROUND: Drug permeation through skin, or a synthetic membrane, from locally acting pharmaceutical products can be influenced by the permeation behaviour of pharmaceutical excipients. OBJECTIVE: Terahertz time-domain technology is investigated as a non-invasive method for a direct and accurate measurement of excipients permeation through synthetic membranes or human skin. METHODS: A series of in-vitro release and skin permeation experiments of liquid excipients (e.g. propylene glycol and polyethylene glycol 400) has been conducted with vertical diffusion cells. The permeation profiles of excipients through different synthetic membranes or skin were obtained using Terahertz pulses providing a direct measurement. Corresponding permeation flux and permeability coefficient values were calculated based on temporal changes of the terahertz pulses. RESULTS: The influence of different experimental conditions, such as the polarity of the membrane and the viscosity of the permeant, was assessed in release experiments. Specific transmembrane flux values of those excipients were directly calculated with statistical differences between cases. Finally, an attempt to estimate the skin permeation of propylene glycol with this technique was also achieved. All these permeation results were likely comparable to those obtained by other authors with usual analytical techniques. CONCLUSION: Terahertz time-domain technology is shown to be a suitable technique for an accurate and non-destructive measurement of the permeation of liquid substances through different synthetic membranes or even human skin.