RESUMEN
Utilization of curcumin has been limited due to its poor oral bioavailability. Oral bioavailability of hydrophobic compounds might be elevated via encapsulation in artificial seed oil bodies. This study aimed to improve oral bioavailability of curcumin via this encapsulation. Unfortunately, curcumin was indissoluble in various seed oils. A mixed dissolvent formula was used to dissolve curcumin, and the admixture was successfully encapsulated in artificial oil bodies stabilized by recombinant sesame caleosin. The artificial oil bodies of relatively small sizes (150 nm) were stably solidified in the forms of powder and tablet. Oral bioavailability of curcumin with or without encapsulation in artificial oil bodies was assessed in Sprague-Dawley male rats. The results showed that encapsulation of curcumin significantly elevated its bioavailability and provided the highest maximum whole blood concentration (Cmax), 37 ± 28 ng/mL, in the experimental animals 45 ± 17 min (t(max)) after oral administration. Relative bioavailability calculated on the basis of the area under the plasma concentration-time curve (AUC) was increased by 47.7 times when curcumin was encapsulated in the artificial oil bodies. This novel formulation of artificial oil bodies seems to possess great potential to encapsulate hydrophobic drugs for oral administration.
Asunto(s)
Química Farmacéutica , Curcumina/farmacocinética , Administración Oral , Animales , Disponibilidad Biológica , Proteínas de Unión al Calcio/metabolismo , Curcumina/administración & dosificación , Masculino , Tamaño de la Partícula , Proteínas de Plantas/metabolismo , Polvos/administración & dosificación , Polvos/química , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/metabolismo , Aceite de Sésamo/química , Comprimidos/administración & dosificación , Comprimidos/químicaRESUMEN
BACKGROUND: Oil bodies isolated from sesame seeds coalesced to form large oil drops when they were solidified in a drying process commonly used for food products. The aim of this study was to develop a protocol to solidify oil bodies for long-term storage at room temperature. RESULTS: On the basis of testing several excipients, the coalescence of oil bodies could be effectively prevented when they were combined with mannitol. Sizes of oil bodies appeared similar under a light microscope before and after powderisation in combination with 70% or more mannitol. Artificial oil bodies were successfully generated with sesame oil, phospholipid and recombinant sesame caleosin. Following the developed protocol, native and artificial oil bodies were stably solidified in tablets. Both native and artificial oil bodies dissolved from the tablets remained stable after an accelerated stress test under a condition of 75% humidity at 40 °C for 4 months. CONCLUSION: A protocol was successfully developed for the solidification of native and artificial oil bodies in stable powder and tablet forms. This successful protocol is very likely to expedite the utilisation of artificial oil bodies in their potential applications.
Asunto(s)
Proteínas de Unión al Calcio/química , Química Farmacéutica , Desecación , Aceites/química , Fosfolípidos/química , Proteínas de Plantas/química , Aceite de Sésamo/química , Sesamum/química , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Manitol/química , Microscopía , Aceites/síntesis química , Polvos/química , Comprimidos/química , TemperaturaRESUMEN
OBJECTIVE: The study evaluates the short term impacts of an intensive control program for the appropriate us of antimicrobials, and to provide a novel strategy for antimicrobial control in inpatient wards in Taiwan. METHOD: In September 2002, a dual intensive antimicrobial control program was implemented within a 921-bed medical center in Taiwan. The study sample included all patients admitted to the medical center during the basal period (October-December 2001) and the intervention period (October-December 2002), where at least one type of parenteral antimicrobial was administered. The sample comprised of 5046 patients during the basal period and 5054 patients during the intervention period. MAIN OUTCOME MEASURE: Analysis of the impact of the intensive antimicrobial control program was undertaken by comparing clinical outcomes, parenteral antimicrobial consumption and bacterial susceptibilities, before and after the establishment of the intensive antimicrobial control program. RESULTS: No statistical differences were found between the basal and intervention periods with regard to either the demographic variables, such as age and gender, or the incidence of nosocomial infections. The clinical outcomes, including length of stay in the medical center, mortality and readmission rates, were also similar for both periods. As compared to the basal period, the consumption of parenteral antimicrobials--in defined daily doses (DDDs) per 100 patient days (PDs)--declined by 13.2% during the intervention period (71.2 vs. 61.8). There were significant increases in the susceptibilities of Pseudomonas aeruginosa to both amikacin and ciprofloxacin, and Serratia spp. to ciprofloxacin (P < 0.05), while all others remained stable. CONCLUSION: This study reports positive responses to intensive antimicrobial control measures among health professionals within a Taiwanese medical center. Following the implementation of the intensive control program, both prescriptions and consumption levels of parenteral antimicrobials were reduced without compromising the clinical outcomes of patients, while the susceptibility patterns of bacterial organisms mostly remained stable. Long-term control of parenteral antimicrobials under such a program may well produce significant benefits for inpatients through the overall rationalization of antimicrobial usage, leading to potential reductions in both the incidence of adverse effects and the burden of resistant organisms. A method of incorporating this intensive control program into a computerized prescription order system is currently under construction.
Asunto(s)
Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/prevención & control , Infección Hospitalaria/prevención & control , Adulto , Anciano , Aminoglicósidos/uso terapéutico , Antiinfecciosos/economía , Infecciones Bacterianas/microbiología , Cefalosporinas/uso terapéutico , Infección Hospitalaria/microbiología , Costos de los Medicamentos , Farmacorresistencia Bacteriana , Revisión de la Utilización de Medicamentos/economía , Revisión de la Utilización de Medicamentos/métodos , Economía Hospitalaria , Eritromicina/uso terapéutico , Femenino , Glicopéptidos/uso terapéutico , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Penicilinas/uso terapéutico , Quinolonas/uso terapéutico , Taiwán , Tetraciclinas/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
Colchicine and 3-hydroxy-3-methy-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are well known to cause myopathy. Myotoxicity is dose-dependent in both drugs; therefore, the onset of symptoms usually takes months or years. We report the case of a patient with chronic renal failure who had been taking simvastatin for 2 years and developed acute weakness 2 weeks after the start of treatment with colchicines for recurrent gout. The electromyography and elevated muscle enzymes indicated that his symptoms were caused by myopathy. When this patient stopped taking both drugs, his weakness resolved rapidly. Acute myopathy induced by combination therapy with colchicines and simvastatin is rare. In patients with chronic renal failure, co-administration of colchicine with simvastatin may accelerate the onset of myopathy because CYP3A4 (part of cytochrome P450) is crucial in the breakdown of both drugs. When adding colchicine to a medication regimen that includes a HMG-CoA reductase inhibitor for patients with renal insufficiency, drugs that are metabolized outside the CYP3A4 system (e.g., fluvastatin and pravastatin) should be selected instead.