ZYIL1 is a nucleotide‐binding oligomerization domain, leucine rich repeat and pyrin domain‐containing 3 (NLRP3) inflammasome inhibitor, which prevents NLRP3‐induced apoptosis‐associated speck‐like protein containing a caspase activation and recruitment domain oligomerization, thus inhibiting NLRP3 inflammasome pathway. We investigated the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of ZYIL1 after single and multiple doses in healthy subjects. The subjects aged 18–55 years were enrolled in 2 different studies: single and multiple ascending dose. Blood/urine samples were collected at designated time points for pharmacokinetic and pharmacodynamic analysis. In the single‐ascending‐dose study, 30 subjects were enrolled (6 subjects each in 5 dose groups). One adverse event was reported during the study. ZYIL1 was well absorbed with median time to maximum plasma concentration at 1–1.5 hours. The exposures were dose proportional across the dose ranges. ZYIL1 is excreted as an unchanged form via the renal route. The mean elimination half‐life was 6–7 hours. In the multiple‐ascending‐dose study, 18 subjects were enrolled (6 subjects each in 3 dose groups). Eleven adverse events were reported by 6 subjects during the study. The accumulation index at steady state for area under the plasma concentration–time curve indicated that ZYIL1 has a marginal accumulation upon repeated dosing. Dose‐proportional exposure was observed across the dose ranges. All subjects showed >90% interleukin (IL)‐1β inhibition in all dose groups for both studies. Inhibition in IL‐1β and IL‐18 was observed throughout the 14 days of treatment in the multiple‐dose study. The safety profile, rapid absorption, marginal accumulation, and significant inhibition of IL‐1β and IL‐18 level support its development for the management of inflammatory disorders.
The growth of the construction industry has expanded the demand for ceramic building products such as ceramic tiles, which constitute essential building materials. Nonetheless, a huge quantity of waste powder is produced during the polishing of ceramic tiles. The disposal of ceramic waste powder is a key environmental concern that needs to be properly addressed. The purpose of this research is to evaluate the potential of recycling ceramic waste powder as a geopolymer binder. The main objective consists of exploring the impacts of two types of ceramic waste powder (vitrified tiles and wall tiles) on the partial substitution of fly ash in geopolymer concrete. For this, concrete was prepared under ambient conditions without oven curing. Slump, compressive strength, split tensile strength, and modulus of elasticity tests were performed to measure the workability and the mechanical properties of the geopolymer concrete. Its durability was evaluated through water absorption and sorptivity tests. The microstructural behavior was investigated using scanning electron microscopy and X-ray diffraction measurements. The investigation revealed that a 15% partial replacement of fly ash by wall-tile ceramic waste powder in geopolymer concrete gave similar compressive strength, a 3% increase in tensile strength, and a 7% improvement in the modulus of elasticity. Partial replacement of fly ash with 15% vitrified ceramic waste powder reduced sorptivity and improved the microstructure of geopolymer concrete. The findings revealed that ceramic waste powder can be used to replace 10–15% of the fly ash in M35 grade structural geopolymer concrete, which can be cured under ambient conditions. Doi: 10.28991/CEJ-2022-08-07-05 Full Text: PDF
This randomized, single‐treatment, 2‐sequence study evaluated the food effect on oral bioavailability of desidustat. Healthy adult male and female subjects were enrolled and randomly assigned to receive desidustat 50 mg orally in a fasting state in one period and a fed state in the other period. A standardized high‐fat, high‐calorie breakfast was served to assess the food effect. The pharmacokinetic results showed that the time to maximum blood concentration of desidustat was delayed significantly (P < .0001) in the fed state compared to the fasting state. The ingestion of food decreased the maximum blood concentration (Cmax) compared to the fasting state (mean Cmax, 3248 ng/mL in the fed state vs 5496 ng/mL in the fasting state). The geometric mean ratio of fed/fasting for log‐normal (ln) Cmax was 57. The exposure decreased in the fed state compared to the fasting state (mean area under the concentration‐time curve [AUC] over the dosing interval, 25 559 ng • h/mL in the fed state versus 33 705 ng • h/mL in the fasting state; mean AUC from time 0 to infinity [AUC0‐∞], 25,910 ng • h/mL in the fed state vs 34 233 ng • h/mL in the fasting state). The geometric mean ratio of fed/fasting for lnAUC from time 0 to the last quantifiable concentration and ln AUC0‐∞ was 77 and 76, respectively. The 90%CI of fed/fasting ratio of the geometric mean of lnCmax, AUC over the dosing interval, and AUC0‐∞ of desidustat 50 mg did not fall within 80%–125% margin. Therefore, the absence of food effect could not be established. It can be inferred that food has a significant effect on the oral absorption of desidustat. Therefore, food must not be consumed 1 hour before and 2 hours after the oral administration of desidustat.
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