Age and sex determine conversion from immediate-release to extended-release tacrolimus in a multi-center cohort of Canadian pediatric renal transplant recipients.

ER-Tac, taken once per day, is associated with improved adherence. This study examined the potential patient and clinical factors that influence clinicians to convert pediatric patients from immediate-release to ER-Tac. This prospective multi-center observational study followed Canadian pediatric kidney transplant recipients up to 5 years post-transplant. Cox Proportional Hazards Regression was used to examine the influence of factors on conversion to ER-Tac. Sixty-six participants were included in this analysis. For every additional year of age at the time of transplant, the likelihood of conversion was more than doubled (HR 2.54, CI 1.83, 3.54, P < 0.001). The impact of age reduced by three percent for every month after transplant (HR 0.97, CI 0.95, 0.98, P < 0.001). Girls were more likely to be converted than boys (HR 3.78, CI 1.35, 10.6, P 0.01). Adherence measures (MAM-MM and tacrolimus trough variability), individual barriers to adherence, renal function, HLA mismatch, and rejection were not significant predictors of conversion in the final regression model. ER-Tac was preferentially prescribed to older age and female patients. Female sex and adolescence are both associated with worse graft outcomes, but we found no link between individualized markers of adherence/graft risk and conversion. Clinicians appeared to be using demographic features to distinguish patients at perceived higher risk and converted accordingly, without a case-by-case evaluation of who is more susceptible to poor outcomes.

Pluronic triblock copolymer systems and their interactions with Ibuprofen.

Small-angle neutron scattering and pulsed-field gradient stimulated-echo nuclear magnetic resonance (NMR) have been used to study the structural characteristics of aqueous Pluronic solutions. In particular, changes in the micellar structure upon addition of ibuprofen to the solutions and altering the temperature have been investigated. Increases in temperature and ibuprofen concentration both appear to favor micellization, with increases observed in the aggregation number, fraction of polymer micellized, and core radius of the micelle, along with a decrease in the volume fraction of the solvent in the core. At high drug concentrations and/or temperatures, micelles of the more hydrophobic Pluronics scatter neutrons strongly at low Q, indicating attractive interactions between micelles or a change in the shape of the aggregates. The addition of ibuprofen to Pluronic P104 has also been found to reduce the critical micellization temperature from approximately 20 degrees C to below 13 degrees C. The hydrophobicity of the Pluronic, quantity of ibuprofen present, and temperature of the solution all seem to have a strong influence on the extent and nature of aggregation observed.

PFGSE-NMR study of pH-triggered behavior in pluronic-ibuprofen solutions.

The effect of drug addition and pH variation on Pluronic copolymer solutions has been investigated using pulsed-field gradient (PFG) NMR. Addition of ibuprofen to Pluronic P104 in solution reduced the overall pH from 7.5 to 4.5, as well as promoting micellization; a substantial increase in the hydrodynamic radius of the micelles, from 57.7 to 102.3 A was observed, along with an increase in the fraction of polymer micellized. The aggregation behavior was attributed primarily to the presence of ibuprofen, rather than the reduction in pH observed, since the micellization of P104 alone was not found to be significantly altered by pH changes in the region of interest. Conversely, for the P104 solutions containing ibuprofen, a strong pH-dependence was observed when raising the pH above the pK(a) of ibuprofen. The data obtained showed that, above pH 4.5, ibuprofen is gradually released from the micelles as a result of its improved solubility, leading to a reduction in the polymer aggregation toward that observed before the addition of ibuprofen.