We report a PopPK model for cyclosporine in Tunisian HSCT patients. Bayesian estimation using only three concentrations provides good prediction of cyclosporine exposure. These tools allow us to routinely estimate cyclosporine AUC in a clinical setting.
Titanate nanotubes
(TiNTs) produced by the static hydrothermal
process present a promising nanosystem for nanomedicine. However,
the behavior of these nanotubes in vivo is not yet clarified. In this
work, for the first time, we investigated the toxicity of these materials,
their pharmacokinetic profile, and their biodistribution in mice.
A high dose of TiNTs (45 mg/kg) was intravenously injected in mice
and monitored from 6 h to 45 days. The histological examination of
organs and the analysis of liver and kidney function markers and then
the inflammatory response were in agreement with a long-term innocuity
of these nanomaterials. The parameters of pharmacokinetics revealed
the rapid clarification of TiNTs from the bloodstream after 6 h of
the intravenous injection which then mainly accumulated in the liver
and spleen, and their degradation and clearance in these tissues were
relatively slow (>4 weeks). Interestingly, an important property
of
these materials is their slow dissolution under the lysosome acid
environment, rendering them biodegradable. It is noteworthy that TiNTs
were directly eliminated in urine and bile ducts without obvious toxicity
in mice. Altogether, all these typical in vivo tests studying the
TiNT pharmacokinetics, toxicity, and biodistribution are supporting
the use of these biocompatible nanomaterials in the biomedical field,
especially as a nanocarrier-based drug delivery system.
Measurements of Cyclosporine (CsA) systemic exposure permit its dose adjustment in allogenic stem cell transplantation recipients to prevent graft-versus-host disease. CsA LSSs were developed and validated from 60 ASCT patients via multiple linear regressions. All whole-blood samples were analyzed by fluorescence polarization immunoassay (FPIA-Axym). The 10 models that have used CsA concentrations at a single time point did not have a good fit with AUC0–12 (R2 < 0.90). C
2 and C
4 were the time points that correlated best with AUC0–12 h, R2 were respectively 0.848, and 0.897. The LSS equation with the best predictive performance (bias, precision and number of samples) utilized three sampling concentrations was AUC0–12 h = 0.607 + 1.569 × C
0.5 + 2.098 × C
2 + 3.603 × C
4 (R2 = 0.943). Optimal LSSs equations which limited to those utilizing three timed concentrations taken within 4 hours post-dose developed from ASCT recipient's patients yielded a low bias <5% ranged from 1.27% to 2.68% and good precision <15% ranged from 9.60% and 11.02%. We propose an LSS model with equation AUC0–12 h = 0.82 + 2.766 × C
2 + 3.409 × C
4 for a practical reason. Bias and precision for this model are respectively 2.68% and 11.02%.
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