CYP1A2 is considered one of the CYPs which collectively are responsible for the metabolism of a number of therapeutically used drug in liver. Recent studies have demonstrated large variability in CYP1A2 activity between individuals, this can lead to reduced therapeutic efficacy and undesired effects in use of several clinically important drugs. The speed of the enzyme reaction of the metabolism caffeine to paraxanthine is applied for phenotyping of CYP1A2. The salivary ratio of paraxanthine to caffeine concentrations in a sample taken approximately 4 hr after a defined dose of caffeine is a more convenient, less expensive but also fully validated CYP1A2 phenotyping metric.
Our goals were to develop population pharmacokinetic model for caffeine and paraxanthine in saliva samples taken after a defined dose of caffeine and to estimate corelation between caffeine clearance and the paraxanthine to caffeine metabolic ratio at 4 hr after administration of caffeine. A simple HPLC assay was used to quantitate caffeine and paraxanthine concentrations in saliva. First we developed simple basic model which include only caffeine concentrations after the different times, then we upgraded the population model with paraxanthine concentrations as the major metabolite. At the end we evaluated the developed population models. For CYP1A2 phenotyping we also determined pharmacokinetic parameters and calculated its variability in population. All statistical analysis were made in statistical program named NONMEM, on the data acquired in research of Illycaffe factory on 18 healthy volunteers.
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