Two-compartment pharmacokinetic model of itraconazole after single oral dose administration - gender differences

Background/Aim. Itraconazole (ICZ) is a widely used antifungal drug with hypervariable pharmacokinetics (PK), which is the result of the molecule?s nature itself, as well as the influence of multiple factors. One of the factors is gender, but its importance is not yet substantiated. The aim of the study was to examine the effect of gender on ICZ PK using a two-compartment model, obtained after a single oral dose of the drug, under fed conditions, in healthy participants of both genders. Methods. A previously conducted bioequivalence study of two pharmaceutical formulations of a 100 mg oral dose of ICZ in 38 healthy participants (22 men and 16 women) yielded 114 sets of ICZ plasma concentrations. Of these, 64 sets (40 from men and 24 from women) were analyzed in this study using Kinetica software as they fit the two-compartment model. ICZ plasma concentrations were determined by a previously validated liquid chromatographic method with mass spectrometric detection. Statistical analyses in SPSS included Mann-Whitney U and Fisher?s exact tests for group comparisons, along with Spearman?s correlation for parameter relationships. Results. Poorer ICZ absorption was observed in females compared to males, accompanied by differences in the drug?s distribution process between the central and peripheral compartments and vice versa. What?s more, there are also differences in ICZ elimination between genders, with it being more effective in women. This isn?t solely a result of a more prominent first-pass effect, but is also connected to the terminal phase of elimination after oral administration of the drug. Conclusion. The application of a two-compartment model for ICZ after its single oral dose administration under fed conditions in healthy research participants provided a more detailed insight into the variable PK of this drug, as well as into the existing gender-based differences.