RESUMEN
Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.
Asunto(s)
Aluminio/metabolismo , Calcio/metabolismo , Ciprofloxacina/metabolismo , Liberación de Fármacos/fisiología , Hierro/metabolismo , Zinc/metabolismo , Aluminio/química , Disponibilidad Biológica , Biofarmacia/métodos , Calcio/química , Ciprofloxacina/química , Interacciones Farmacológicas/fisiología , Hierro/química , Solubilidad , Difracción de Rayos X/métodos , Zinc/químicaRESUMEN
Experimental autoimmune encephalomyelitis (EAE) is characterized by appearance of anti-myelin autoantibodies in the blood and with the increased expression of MHC (major histocompatibility complex) class I and II antigens in the brain tissue. Although there is an evidence of possible linkage between influenza vaccination and development of autoimmune processes, the precise mechanisms of action of this vaccine on EAE-induction is still unclear. In this study, effects of influenza vaccine on clinical sign, antimyelin antibody titer in the blood by ELISA test and expression of MHC class I and II molecules immunohistochemistry were examined in the brain of C57BL mice with EAE. EAE was induced by MOG 35-55 protein in 16 of 32 mice. Influenza split vaccine was administered to eight MOG-induced EAE mice and to eight previously nontreated mice. A significant increase of anti-influenza antibody was detected in vaccinated mice compared to nontreated mice. Also, significant increase of antimyelin antibodies was detected in mice with EAE compared to vaccinated group without EAE and control group, respectively. In EAE-influenza vaccinated mice, a mild but not significant increase of antimyelin antibodies was detected, compared to EAE mice. High expression of MHC-II and mild expression of MHC-I were detected in the brain of mice with EAE. No expressions were detected in vaccinated and normal intact brains. Similar staining was found between EAE-vaccinated and EAE group in both MHC-I and MHC-II expression. The results obtained show that influenza vaccine has no significant influence on EAE induction and severity of autoimmune processes.
Asunto(s)
Autoinmunidad/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Vacunas contra la Influenza/inmunología , Animales , Autoanticuerpos/sangre , Autoinmunidad/efectos de los fármacos , Encéfalo/inmunología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Femenino , Vacunas contra la Influenza/uso terapéutico , Complejo Mayor de Histocompatibilidad/inmunología , Ratones , Vaina de Mielina/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/uso terapéuticoRESUMEN
With the development of physiologically based absorption models, there is an increased scientific and regulatory interest in in silico modelling and simulation of drug-drug and drug-food interactions. Clinically significant interactions between ciprofloxacin and metallic compounds are widely documented. In the current study, a previously developed ciprofloxacin-specific in silico absorption model was employed in order to simulate ciprofloxacin/metallic compound interaction observed in vivo. Commercially available software GastroPlus™ (Simulations Plus Inc., USA) based on the ACAT model was used for gastrointestinal (GI) simulations. The required input parameters, relating to ciprofloxacin hydrochloride physicochemical and pharmacokinetic characteristics, were experimentally determined, taken from the literature or estimated by GastroPlus™. Parameter sensitivity analysis (PSA) was used to assess the importance of selected input parameters (solubility, permeability, stomach and small intestine transit time) in predicting percent drug absorbed. PSA identified solubility and permeability as critical parameters affecting the rate and extent of ciprofloxacin absorption. Using the selected input parameters, it was possible to generate a ciprofloxacin absorption model, without/with metal cation containing preparations co-administration, which matched well the in vivo data available. It was found that reduced ciprofloxacin absorption in the presence of aluminium hydroxide, calcium carbonate or multivitamins/zinc was accounted for by reduced drug solubility. The impact of solubility-permeability interplay on ciprofloxacin absorption can be observed in the ciprofloxacin-aluminium interaction, while in ciprofloxacin-calcium and ciprofloxacin-zinc interactions, effect of solubility was more pronounced. The results obtained indicate that in silico model developed can be successfully used to complement relevant in vitro studies in the simulation of physicochemical ciprofloxacin/metallic compound interactions.
Asunto(s)
Ciprofloxacina/química , Metales/química , Modelos Biológicos , Ciprofloxacina/farmacocinética , Simulación por Computador , Absorción Gastrointestinal , Metales/farmacocinéticaRESUMEN
The ciprofloxacin-iron interaction, resulting in a lower bioavailability, is well documented in vivo; however, a mechanistic explanation supported by experimental data of this interaction is missing. In the present study, ciprofloxacin hydrochloride (HCl) and ferrous sulfate interaction was simulated in vitro by performing solubility and dissolution studies in the reactive media containing ferrous sulfate. Characterization of the precipitate formed indicated its probable chemical structure as Fe(SO(4) (2-) )(2) (Cl(-) )(2) (ciprofloxacin)(2) × (H(2) O)(n) , where n is up to 12 molecules of water. The solubility of this complex in water was estimated to be approximately 2 mg/mL, being about 20-fold lower than the solubility of ciprofloxacin HCl. The solubility of the complex was used as input parameter for an in silico modeling by GastroPlus™ and the resulting predicted plasma time curves were in good agreement with the in vivo data. These results strongly indicate that ciprofloxacin-iron interaction in vivo is caused by the formation of a low soluble complex. This interaction was also simulated by in vitro dissolution, in which a mini scale apparatus provided more biorelevant results than the standard dissolution apparatus, probably because the drug concentrations in the mini apparatus were higher and, thus, closer to the conditions encountered in vivo.
Asunto(s)
Antiinfecciosos/metabolismo , Ciprofloxacina/metabolismo , Simulación por Computador , Compuestos Ferrosos/metabolismo , Antiinfecciosos/química , Disponibilidad Biológica , Cloruros/análisis , Ciprofloxacina/química , Computadores , Interacciones Farmacológicas , Compuestos Ferrosos/química , Modelos Químicos , Programas Informáticos , Solubilidad , Sulfatos/análisisRESUMEN
BACKGROUND: Sarcoidosis is a chronic inflammatory disease, commonly found in lungs and hilar lymph nodes, but multiple organs could be involved. The diagnosis is based on specific pathohistology which should be always combined with clinical, radiological and laboratory findings. CASE REPORT: A patient initially presented with pneumonia, and treated with antibiotics, but with the general symptoms that persisted despite radiological resolution of lung infiltration was reported. The further diagnostic procedures revealed the presence of sarcoid granulomas in cervical lymph nodes. The peripheral lymph nodes are often affected in the early course of the disease, but it is difficult to distinguish if the illness is a sarcoid reaction to lung infection or a acute onset of sarcoidosis. CONCLUSION: The detection of sarcoid granulomas in cervical lymph nodes should be precisely analyzed for the presence of sarcoidal changes in other tissues, primarily in the lungs tissue. Early diagnosis of lung sarcoidosis is significant, especially in the light of the fact that the latest studies point out that the prednisone therapy, started immediately after the diagnosis has been made, renders positive effects also in asympthomatic patients in II and III phase of the disease.