To compare individual case safety reports (ICSR) rates and characteristics between Croatia, Serbia, Montenegro, and Bosnia and Herzegovina (B&H).This retrospective pharmacoepidemiological study used the data from ICSR received by the Agency for ...

Dissolution Profile of Nimesulide from Pharmaceutical Preparations for Oral Use

Cytochrome P450 (CYP450) enzymes are pivotal in the metabolism of numerous anticancer agents, with CYP3A4 being the predominant isoform involved. Inhibition of CYP450 enzymes is a major mechanism underlying clinically significant drug-drug interactions (DDIs), particularly in oncology, where polypharmacy is frequent. This review aims to provide a comprehensive and critical overview of CYP450 enzyme inhibition, focusing specifically on the impact of kinase inhibitors (KIs) and poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. A systematic review of the current literature was conducted, focusing on the molecular mechanisms of CYP450 inhibition, including reversible, time-dependent, mechanism-based, and pseudo-irreversible inhibition. Specific attention was given to the inhibitory profiles of clinically relevant KIs and PARP inhibitors, with analysis of pharmacokinetic consequences and regulatory considerations. Many KIs, such as abemaciclib and ibrutinib, demonstrate time-dependent or quasi-irreversible inhibition of CYP3A4, while PARP inhibitors like olaparib and rucaparib exhibit moderate reversible and time-dependent CYP3A4 inhibition. These inhibitory activities can significantly alter the pharmacokinetics of co-administered drugs, leading to increased risk of toxicity or therapeutic failure. Regulatory guidelines now recommend early identification of time-dependent and mechanism-based inhibition using physiologically based pharmacokinetic) (PBPK) modeling. CYP450 inhibition by KIs and PARP inhibitors represents a critical but often underappreciated challenge in oncology pharmacotherapy. Understanding the mechanistic basis of these interactions is essential for optimizing treatment regimens, improving patient safety, and supporting personalized oncology care. Greater clinical vigilance and the integration of predictive modeling tools are necessary to mitigate the risks associated with CYP-mediated DDIs.

The pharmacological potential of Lamiaceae plants is primarily linked to their high content of phenolic acids and flavonoids, known for strong antioxidant properties. This study investigated the antioxidant activity of ten widely used Lamiaceae herbs—oregano, lavender, basil, savory, garden thyme, wild thyme, sage, rosemary, lemon balm, and mint—prepared as traditional infusions and microwave-assisted extracts. The antioxidant capacity was evaluated using spectrophotometric assays, and total phenolics and flavonoids were quantified via spectrophotometry and HPLC. Chemometric analysis (PCA) was applied to explore correlations among antioxidant parameters. The results demonstrated excellent antioxidant activity across all samples. The IC50 for DPPH radicals was in the range from 3.73(0.13) to 8.03(0.17) μg/mL and that for ABTS radicals was from 2.89(0.12) to 8.55(0.34). The CUPRAC antioxidant assay delivered values in the range from 351.93(11.85) to 1129.68(44.46) μg TE/mg DE. The FRAP method produced values from 1.27(0.03) to 6.60(0.26) μmol Fe/mg DE. The presence of gallic acid was detected in all examined samples, with lemon balm and lavender exhibiting the highest concentrations across both applied extraction methods. Notably, lavender showed especially high levels of p-hydroxybenzoic acid and chlorogenic acid. Microwave-assisted extraction generally yielded higher levels of bioactive compounds compared to infusion. These findings highlight the potential of Lamiaceae herbal extracts, particularly those obtained through microwave-assisted extraction, as valuable sources of dietary antioxidants for everyday use.

A series of new (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography—tandem mass spectrometry (UHPLC—MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL⁻¹ for DE-EDCP and 0.3 μg mL⁻¹ for EDCP. The calibration curves were linear over the concentration range of 1.3–26.7 ng mL⁻¹ and 0.3–6.7 μg mL⁻¹ for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (%RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC—MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.