Preparation of Cinacalcet Nanoemulsion and Its In Vivo and In Vitro Evaluation / 中国药学杂志

OBJECTIVE: To improve the dissolution and oral bioavailability of cinacalcet in fasted state by preparing cinacalcet nanoemulsion. METHODS: The oil phase, emulsifiers and co-emulsifiers were selected by solubility test and phase diagram studies. The dissolution in vitro and bioavailability in Bealge dogs of cinacalcet nanoemulsion were evaluated. RESULTS: The cinacalcet nanoemulsion was prepared with oleic acid(as oil phase), OP-10 (as emulsifier), PEG200 (as co-emulsifier) and water (W-W=3:8:4:15) and showed goog physical properties with regular round appearance. The average particle size of cinacalcet nanoemulsion was (24.1±3.8) nm. The poly-dispersity index (PDI) and Zeta potential were (0.261±0.032) and (-26.1±1.7) mV, respectively, which proved that the cinacalcet nanoemulsion formed a stable system. The in vitro dissolution of cinacalcet was significantly improved after being prepared into nanoemulsion. The pharmacokinetic study showed that the bioavailability of cinacalcet nanoemulsion was significantly enhanced in Beagle dogs in fasted state and the absorbtion of cinacalcet nanoemulsion had no difference in fed and fasted state. CONCLUSION: Cinacalcet nanoemulsion is easy to prepare and has small particle size, which can significantly improve the dissolution and bioavailability of cinacalcet in fasted state.

Effects of starvation, diabetesand obese conditions on mouse hepatic SOCS2 gene expression / 基础医学与临床

Objective To determine the expression levels of SOCS2 in the mouse livers under starvation, diabetes and obese conditions and to study the effect of SOCS2 on gluconeogenesis.Methods Animals were divided into 3 groups: C57BL/6J mice, the control group was fed ad libtum and the experimental group was fasted for 24 h.Diabetes model db/db and the control db/m mice were fed ad libitum.Obese model ob/ob and the control C57BL/6J mice were fed ad libitum.All the mice above were sacrificed and total RNA was isolated from mouse livers and reverse transcribed to cDNA.The expression of SOCS2 and gluconeogenesis genes in the mouse livers in the 3 groups above were detected by real-time quantitative PCR.SOCS2 was overexpressed in the primary C57BL/6J mouse hepatocytes by the adenovirus system.The effect of SOCS2 on glucose production was measured by glucose output assay.Results C57BL/6J mouse hepatic SOCS2 expression was suppressed by starvation status.The expression of SOCS2 was decreased in the livers of db/db and ob/ob mice.In contrast, the key regulators of gluconeogenesis, PGC-1α, PEPCK and G6Pase exhibited the opposite expression pattern as SOCS2 in the livers underidentical starvation, diabetes and obese conditions.The protein was Mr 23 000 and glucose production was inhibited after SOCS2 being overexpressed in the primary C57BL/6J mouse hepatocytes by adenovirus system.Conclusions SOCS2 may inhibit gluconeogenesis in the C57BL/6J mouse primary hepatocytes, and SOCS2 may be a potential target for the treatment of type Ⅱ diabetes.

Beneficios metabólicos de realizar ejercicio en estado de ayuno / Metabolic benefits of exercise in the fasted state

The high rate of obesity in sedentary population, coupled with the increase in diseases associated with this lifestyle, have led us to seek new strategies to enhance the physical training that will favor mobilization, uptake and utilization of fats and glucose. Doing exercise in the fasted state is one that has proved more promising. There is sufficient evidence on the benefits of physical activity during fasting producing a favorable hormonal environment, activation of mediators such as AMPKand LPL activation, among others. Performing aerobic exercise of moderate intensity in this environment favors fasting lipid oxidation, decreasing intramyo-cellular triglycerides, visceral fat and LDL cholesterol, compared with the benefits of exercise in the postprandial state. There is an important need for more studies of physical activity in the fasted state that include patients with chronic non-transmissible diseases and resistance training.

El alta tasa de obesidad y sedentarismo de la población, sumado al aumento de las patologías asociadas a éste estilo de vida, nos han llevado a buscar nuevas estrategias de entrenamiento físico que potencien la movilización, captación y utilización de grasas y glucosa. La realización de ejercicio en estado de ayuno es una de las que ha resultado ser más promisoria. Hay evidencia suficiente sobre los beneficios de realizar actividad física en ayunas, ya sea por el ambiente hormonal favorable, la activación de mediadores como el AMPK y la activación de la LPL, entre otros. La realización de ejercicio aeróbico de intensidad moderada en este ambiente de ayuno favorece la oxidación de lípidos, la disminución de los triglicéridos intramiocelulares, la grasa visceral y del colesterol LDL, en comparación con los beneficios del ejercicio realizado en ambiente postprandial. Existe una necesidad de un mayor número de estudios con actividad física en ayuna, donde se incluya a paciente con enfermedades crónicas no transmisibles y los ejercicios de tipo resistido.

Steady-State Pharmacokinetic Properties of Tamsulosin in Healthy Male Volunteers

BACKGROUND: To evaluate the pharmacokinetic properties of daily oral doses of tamsulosin administered to fasted healthy Korean male volunteers for 5 days. METHODS: In a randomized, open-label, multiple-dose, two-period, crossover study, all 44 subjects were randomly assigned in a 1:1 ratio to receive a newly developed generic capsule formulation (test) or a branded capsule formulation (reference) of tamsulosin 0.2 mg, followed by a 10-day washout period and administration of the other formulation. Plasma concentrations of tamsulosin were assessed after administration of five-day multiple doses, using HPLC-MS/MS. Clinical and laboratory adverse events (AE) were assessed. RESULTS: The mean (SD) pharmacokinetic properties with the test and reference formulations were as follows: Css,max, 9.0 (2.9) and 8.4 (2.6) ng/mL, respectively; median (range) tmax, 4 (2-6) and 5 (2-7) hours; AUCtau, 93.7 (31.5) and 88.2 (29.3) ng x h/mL; and t(1/2), 9.5 (2.6) and 10.0 (2.7) hours. The volume of distribution and clearance after oral administration of tamsulosin were 0.5 L/kg, and 0.04 L/h/kg, respectively. The accumulation ratios for 0.2 mg once-daily dosing regimen were 1.2. The 90% CIs of the geometric mean ratios for the log-transformed AUCtau (1.005-1.131) and Css,max (1.000-1.136) values were within the acceptable range for bioequivalence. No serious AE was reported during the study. Both formulations were well tolerated. CONCLUSION: The results demonstrate that the Css,max and AUCtau values in the fasted subjects were higher than those in the fed from other study, with a shorter tmax values.