sivakumar v

Achieving and maintaining optimal tacrolimus trough levels for immunosuppression is challenging in kidney transplant patients due to its narrow therapeutic index. Ketoconazole is known for inhibiting the drug efflux activity of P-glycoprotein and CYP3A enzymes, which are involved in tacrolimus pharmacokinetics. Therefore, there is a need to investigate tacrolimus–ketoconazole coadministration. The study aims to assess the effect and safety of tacrolimus-ketoconazole coadministration in renal transplant recipients. Ethical approval was obtained from the Institutional Human Ethics Committee (IHEC/2023/038) to conduct an ambispective observational study on 14 renal transplant recipients. Tacrolimus total daily dose (TDD) and trough levels were measured before and after initiating oral ketoconazole. The concentration/dose (C0/D) ratio was calculated, followed by safety assessments, including blood counts and renal function tests. Statistical analyses employed paired t-tests, and the significance level was <0.05. Coadministration resulted in a significant 102.45% increase in tacrolimus trough levels (p<0.001) and a 2.19% reduction (p=0.33) in TDD. The C0/D ratio showed a mean increase of 127.74%. Blood counts remained within normal ranges, but a significant decrease in sodium (p=0.01) and an increase in potassium (p=0.03) were observed within the normal range. Tacrolimus-ketoconazole co-administration in renal transplant recipients demonstrated a substantial elevation in tacrolimus trough levels, suggesting a potential strategy for achieving therapeutic concentrations without escalating tacrolimus doses. Despite significant changes in sodium and potassium, they remained within acceptable ranges, supporting the safety of this coadministration strategy.

Coccinia Indica (L.) fruit (CIFs) is a mounting, herbaceous, branching latitude vascular domestic plant in Asia, including India. It is a popular medicine for reducing high levels of blood glucose. This work aimed to appraise the photochemical, liquid, gaseous, and solid substances using Gas chromatography and Mass spectroscopy and find the aldose reductase inhibitor (ARI) activity through in-vitro assay using CIFs extracts. CIFs were extracted using polar and non-polar solvents. The results indicated that the ethanolic had a high yield of 33.9% when compared to 18.6% aqueous, 11.3% chloroform, 9.2% petroleum, and also the ethanolic extracts showing maximum phenolic (12.5±0.84mg GAE/g) and flavonoids (78.4±3.6mg QE/gm) dry extract content. GC-MS analysis of the ethanolic extract shows a total of 23 peaked compounds. The in-vitro aldose reductase inhibitor activity was performed with a partly purified bovine lens and revealed that ethanolic extract of CIFs established a 78.46% ARI activity at IC50 value 2.34µg/mL followed by aqueous 76.88% by IC50 value 3.88 µg/mL. Furthermore, the in-silico molecular docking and Density Functional Theory for peak compound was carried out. The CIFs are, therefore, a possible efficient agent with ARI and can be used to manage diabetic mellitus and its accompanying complications.