CYP1A2 -163A/A genotype influence carbamazepine pharmacokinetics. In addition to sex and total carbamazepine daily dose, -163C > A CYP1A2 polymorphism should be considered as a predictor of carbamazepine clearance.

Background: The number of adolescents who use caffeine is constantly increasing. As juvenile age is vulnerable, it is reasonable to expect that they will differently perceive reason and react to caffeine use than adults, and be more prone to unwanted physiological and psychological consequences of its consumption. Aim: Analysis of the scope and pattern of caffeine consumption among adolescents in Serbia. Study design: The cross-sectional survey was implemented in the study population of 191 Serbian adolescents during 2010. Results: The median daily intake of caffeine was 95.6 mg. The major source of caffeine was brewed coffee, and the most common reasons for caffeine intake were leisure, peer influence, or habit. Only 57.6% of the subjects were aware that caffeine is present in consumed beverages. Sex affected the pattern, but not the overall level, of caffeine consumption. No association between caffeine consumption and smoking status, frequency of caffeine use in the family, or negative personal experience with caffeine effects was observed. Conclusion: Our investigation provides first and rather detailed insight into caffeine-containing beverage consumption scope and pattern among Serbian adolescents. For accurate estimation and analysis of caffeine intake in this population, randomized studies with prospective longitudinal design, caffeine content measurement, and more subjects involved are warranted.

Carbamazepine exhibits significant inter-individual variability in its efficacy

Valproate represents one of the most commonly used anticonvulsants worldwide, whose narrow therapeutic range and high potential for drug-drug interactions leads to pronounced intra- and inter-individual variability in plasma concentration and response. The aim of our study was to apply population pharmacokinetics analysis to comprehensively investigate and detect the most important factors affecting pharmacokinetics of valproate in Serbian children with epilepsy. This retrospective observational study was based on demographic and medical data retrieved from the medical records on epileptic patients treated with valproate at the pediatric department of the Clinical Centre, Kragujevac, Serbia. Valproate serum concentrations were obtained as a part of routine medical practice. Population pharmacokinetics analysis was performed by MonolixSuite 2019R1 (Lixoft, Antony, France) software, using one-compartment model with first order absorption and linear elimination. The study included 1642 valproate concentrations obtained from 232 patients, of which 201 (1420 concentrations) were included in the index set used for the modelling, while the other 31 (222 concentrations) were the validation set used for external validation of the final model. Covariate testing based on the whole index set revealed that only total daily valproate dose significanly affected the clearance of valproate: Cl (l/h)= 0.135×1.002DD. When only compliant patients were included, co-treatment with carbamazepine was shown to be of significance as well: Cl(l/h)=0.121×1.002DD×1.2CBZ. Our study demonstrated that valproate clearance correlates with total valproate daily dose. The influence of co-treatment with carbamazepine on valproate pharmacokinetics can be observed and used for clearance estimation only in compliant patients.

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