Current Drug Metabolism - Volume 24, Issue 11, 2023

In silico tool is the flourishing pathway for Researchers and budding chemists to strain the analytical data in a snapshot. Traditionally, drug research has heavily relied on labor-intensive experiments, often limited by time, cost, and ethical constraints. In silico tools have paved the way for more efficient and cost-effective drug development processes. By employing advanced computational algorithms, these tools can screen large libraries of compounds, identifying potential toxicities and prioritizing safer drug candidates for further investigation. Integrating in silico tools into the drug research pipeline has significantly accelerated the drug discovery process, facilitating early-stage decision-making and reducing the reliance on resource-intensive experimentation. Moreover, these tools can potentially minimize the need for animal testing, promoting the principles of the 3Rs (reduction, refinement, and replacement) in animal research. This paper highlights the immense potential of in silico tools in revolutionizing drug research. By leveraging computational models to predict drug metabolism, pharmacokinetics, and toxicity. Researchers can make informed decisions and prioritize the most promising drug candidates for further investigation. The synchronicity of In silico tools in this article on trending topics is insightful and will play an increasingly integral role in expediting drug development.

Background: Decarboxymethyl ligstroside aglycone (Oleocanthal) is an essential component of olive oil. It is therefore interesting to study its metabolism in the human body. In order to find the best possible starting point for this metabolism, a theoretical study was carried out using DFT calculations and docking studies.Methods: The DFT, B3LYP/6-311++G** and the PCM solvation model calculations were used to study the initial process of Oleocanthal metabolism by the CYP1A2 enzyme. Structures of radicals formed by homolytic dissociation of hydrogen atoms from the Oleocanthal structure were obtained and their properties were studied. Several parameters such as HOMO and LUMO energy gaps, Bond Dissociation Energy (BDE), hardness, and spin density of possible Oleocanthal radicals were taken into account. Docking of Oleocanthal into an enzyme binding pocket was also performed to locate the most probably metabolic site. Detailed analysis of the theoretical results allows the determination of the most likely reaction sites in Oleocanthal. The mode of binding of Oleocanthal to the CYP1A2 enzyme was also predicted.Results: The results of the molecular docking studies are in agreement with the calculated quantum parameters. The theoretical predictions were compared with experimental data available in the scientific literature. A high correlation between theoretical calculations and experimental data was observed. The most likely site of Oleocanthal metabolism was identified.Conclusion: The results of our research support the usefulness of theoretical calculations in predicting metabolic pathways.

Aim: This study was aimed to re-determine the radiation dose rate emitted from the patients who underwent bone scintigraphy.Material and Methods: A mean of 20.87±2.54 mCi ^99mTc-MDP was injected into patients. A GM counter was used to measure dose rates in 3 different periods, at intervals of 25, 50, 100, 150, and 200 cm from the patient's anterior for head, thorax, abdomen, and pelvis levels. Measurements were used to determine patient-induced environmental doses and radiation doses to personnel/patient relatives.Results and Discussion: There were strong correlations between mean dose rate (mRh^-1mCi^-1) and time at all regions and distances. The received dose for staff was calculated between a range of 0.01-0.02 mSv/mCi per patient. The total dose to be received by the companion was estimated to be between 0.019-0.039 and 0.011-0.022 mSv for public and personal vehicle transportation, respectively. The radiation dose exposed by nurses (4th, 6th, and 8th hours after injection) was found to be 0.012-0.064, 0.006-0.038, and 0.002-0.018 mSv/- patient, respectively.Conclusion: The fact that the doses of personnel and patient relatives in the study were below the legal limits shows that the study was carried out within a safe range. However, in terms of radiation protection, it is necessary to limit the time spent with the patient as much as possible and increase the distance. Since the dangers of low radiation dosages are unknown, there is a need to inform the patient's relatives and staff about the potential risks.

Background: 101BHG-D01, a novel long-acting and selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD), is undergoing Phase Ib clinical trial in patients and has shown its potential efficacy. Its preparation method and medical use thereof have been patented in the United States (Patent No.US9751875B2).Objective: In this study, the pharmacokinetics, mass balance, tissue distribution and metabolism of radioactive 101BHG-D01 were investigated in rats after an intravenous dose of 1 mg/kg [¹⁴C]101BHG-D01 (100 μCi/kg).Methods: Radioactivity in rat plasma, urine, feces, and tissues was measured by liquid scintillation counting (LSC), and metabolite profiling and identification were conducted by UHPLC-β-RAM and UHPLC-Q-Exactive Plus MS.Results: The total radioactivity of the study drug in rat plasma rapidly declined with an average terminal elimination half-life of 0.35 h. The radioactivity in most tissues reached the maximum concentration at 0.25 h post-- dosing. The radioactivity mainly concentrated in the kidney and pancreas. The drug-related substances tended to be distributed into the blood cells in the circulation. At 168 h post dosing, the mean recovery of the total radioactivity in urine and feces was 78.82%. Fecal excretion was the major excretion route, accounting for approximately 61% of the radioactive dose. The study drug was metabolized extensively, and a total of 17 metabolites were identified in rat plasma, urine, and feces. The major metabolic pathways involved oxidation, oxidation and dehydrogenation, and O-dephenylation.Conclusion: In conclusion, the study results are useful for better understanding the pharmacokinetic profiles of 101BHG-D01 and provide a robust foundation for subsequent clinical studies.

Background: Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target- age animals.Objective: To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. Methods: The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC–UV and analyzed using a non-compartmental method. Results: ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t 1/2#142;zand V dsswere significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in Cl Tand AUC values in different age groups. AUC 0-∞CIP/AUC 0-∞ENRratios were higher in one-month-old than in six- and twelve-months sheep. Conclusion: The most important pharmacokinetic changes associated with aging in sheep are decreased V dssand t 1/2#142;zof ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC 0–24/MIC 90ratios for E. coli, P. multocidaand Mycoplasmaspp. (>125) with MIC of 0.37 μg/mL and for S. aureus (>30) with MIC of 0.5 μg/mL in all ages of sheep.