RESUMEN
The synthesis and properties of thermal/pH-sensitive core-shell copolymer nano/microgels were investigated. The crosslinked core consisted of N-isopropylacrylamide (NIPAAm) while the shell was stabilized by poly(ethylene glycol) methyl ether methacrylate (PEGMA) and 2-methacryloyloxybenzoic acid (2MBA) using a "one pot" soapless emulsion polymerization method. Monodisperse particles were produced with average hydrodynamic diameters ranging from 40 to 880 nm, as determined by dynamic light scattering (DLS) in water at 25°C, depending on the synthetic recipe used. The influence of PEGMA and 2MBA content on size and temperature transition at different pH values was studied. Zeta potential measurements and acid-base titration studies demonstrated almost complete incorporation of acid comonomer (2MBA) into the nano/microgels. Two different crosslinkers, a stable and an acid labile, were compared. The crosslinker used has a major influence on the size and charge density of the nano/microgels produced. Microscopic studies confirmed the core-shell morphology of the nano/microgels.
RESUMEN
PURPOSE: A vancomycin population pharmacokinetic prediction model for adult and elderly patients was developed using NONMEM. The predictability of the model was studied and compared with ten other models. METHODS: Data were collected from routine care of 141 subjects. NONMEM was used to derive a population model. After internal evaluation using the bootstrap technique, external validation was studied using an independent dataset that consisted of 95 subjects; a statistical comparison of precision and bias was conducted. RESULTS: A two-compartment open model was derived with body weight, age, and CLcr as covariates. The bootstrap process showed stability of the model. A comparison of subjects older and younger than 65 years found that the older group had a mean clearance of 2.24 (+/- 1.2) l/h compared to 4.03 (+/- 1.7) l/h, and a peripheral volume of 43.7 (+/- 5.1) l compared to 28.4 (+/- 5.3) l compared to younger patients. These values were modeled using CLcr in the clearance equation and Vd as a function of age. The eleven models studied showed a bias in predicting serum concentrations from the test database that ranged from 0.35 mg/l to -5.93 mg/l. Precision ranged from 4.53 mg/l to 8.05 mg/l. Our method ranked in fourth place overall and when compared statistically its bias was different from the method that ranked in second place by -1.45 (95% CI -2.46, -0.42; p = 0.005), and different from all the methods that ranked worse. The only difference in precision was with the method that ranked in eleventh place with a relative precision of 0.49 (95% CI 0.27, 0.70; p < 0.001). CONCLUSIONS: A two-compartment open model fitted the data with weight, age, and CLcr as covariates. The derived method ranked in fourth place overall. The two-compartment nature of two of the equations studied did not provide an advantage. A future study with more data in the distribution phase could provide a model with better predictability.