Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

Galectin-3 (Gal-3) plays a multifaceted role in the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). This review offers a comprehensive examination of its expression in PDAC, its interaction with various immune cells, signaling pathways, effects on apoptosis, and therapeutic resistance. Additionally, the prognostic significance of serum levels of Gal-3 is discussed, providing insights into its potential utilization as a biomarker. Critical analysis is also extended to the inhibitors of Gal-3 and their potential therapeutic applications in PDAC, offering new avenues for targeted treatments. The intricate nature of Gal-3’s role in PDAC reveals a complex landscape that demands a nuanced understanding for potential therapeutic interventions and monitoring.

The aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.