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Aim: To develop a pharmacokinetic/pharmacodynamic (PK/PD) model describing the receptor/gene-mediated induction of CYP3A1/2 by dexamethasone (DEX) in rats. Methods: A group of male Sprague-Dawley rats receiving DEX (100 mg/kg, ip) were sacrificed at various time points up to 60 h posttreatment. Their blood sample and liver were collected. The plasma concentration of DEX was determined with a reverse phase HPLC method. CYP3A1/2 mRNA, protein levels and enzyme activity were measured using RT-PCR, ELISA and the testosterone substrate assay, respectively. Data analyses were performed using a first-order conditional estimate (FOCE) with INTERACTION method in NON-MEM version 7.1.2. Results: A two-compartment model with zero-order absorption was applied to describe the pharmacokinetic characteristics of DEX. Systemic clearance, the apparent volume of distribution and the duration of zero-order absorption were calculated to be 172.7 mL·kg --1 ·h -1 , 657.4 mL/kg and 10.47 h, respectively. An indirect response model with a series of transit compartments was developed to describe the induction of CYP3A1/2 via PXR transactivation by DEX. The maximum induction of CYP3A1 and CYP3A2 mRNA levels was achieved, showing nearly 21.29-and 8.67-fold increases relative to the basal levels, respectively. The CYP3A1 and CYP3A2 protein levels were increased by 8.02-fold and 2.49-fold, respectively. The total enzyme activities of CYP3A1/2 were shown to increase by up to 2.79-fold, with a lag time of 40 h from the Tmax of the DEX plasma concentration. The final PK/PD model was able to recapitulate the delayed induction of CYP3A1/2 mRNA, protein and enzyme activity by DEX. Conclusion: A mechanism-based PK/PD model was developed to characterize the complex concentration-induction response relationship between DEX and CYP3A1/2 and to resolve the drug-and system-specific PK/PD parameters for the course of induction.

Cellulose films are regarded as sustainable materials having wide applications in food packaging, separation, etc. Their preparation substantially relies on sufficient dissolution. Herein, various celluloses adequately dissolved in a new solvent system of carbon dioxide,1, 8-diazabicyclo [5.4.0] undec-7-ene and dimethyl sulfoxide (CO2/DBU/DMSO) were made in to films using different regeneration reagents. The films regenerated from ethanol and methanol presented homogeneous and smooth surfaces, while those from 5 wt % NaOH (aq.) and 5 wt % H2SO4 (aq.) showed rough surfaces, as analyzed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The films regenerated from 5 wt % NaOH (aq.) and 5 wt % H2SO4 (aq.) rendered cellulose II structures, while those regenerated from alcohols had amorphous structures as evidenced using fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) results. The films made of microcrystalline cellulose had a good light transmittance of about 90% at 800 nm with a tensile strength of 55 MPa and an elongation break of 6.5%, while those from wood pulp cellulose demonstrated satisfactory flexibility with a tensile strength of 91 MPa and an elongation break of 9.0%. This research reports a simple, environmental, and sustainable method to prepare cellulose films of good mechanical properties.

A biobased polyelectrolyte was prepared and used successfully as a precursor for the fabrication of N-doped hierarchically porous carbon materials with tunable electrochemical properties in supercapacitors.