RESUMEN
A sensitive and selective reversed-phase liquid chromatographic assay for itraconazole and hydroxyitraconazole in human plasma has been developed and validated. Itraconazole and hydroxyitraconazole were extracted from the matrix using solid-phase extraction on a strong cation-exchange sorbent. All compounds were detected using fluorescence at 265 and 363 nm for excitation and emission, respectively. The assay has been validated over the range 10-1,000 ng/ml for both compounds, 10 ng/ml being the lower limit of quantification. Accuracies ranged from 104 to 113% for itraconazole and from 91 to 103% for hydroxyitraconazole. The intra-assay precisions were all below 9% for itraconazole and below 8% for hydroxyitraconazole. The selectivity has been evaluated with respect to all registered anti-human immunodeficiency virus (HIV) drugs and other potential co-medications and a few of their metabolites, commonly used by HIV-infected individuals. Both itraconazole and hydroxyitraconazole were stable under relevant conditions for HIV-inactivation and storage of samples. The applicability of the assay was demonstrated for samples collected from a treated HIV-infected patient.
Asunto(s)
Antifúngicos/sangre , Cromatografía Líquida de Alta Presión/métodos , Infecciones por VIH/sangre , Itraconazol/análogos & derivados , Itraconazol/sangre , Antifúngicos/farmacocinética , Humanos , Itraconazol/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de FluorescenciaRESUMEN
The authors describe the development of a population pharmacokinetic model using NONMEM for itraconazole and its active metabolite hydroxyitraconazole in a Thai cohort of HIV-infected patients who were using itraconazole as an addition to their antiretroviral therapy. The data were best described with an open two-compartment model for both itraconazole and hydroxyitraconazole. The model adequately described the data and provided population pharmacokinetic parameters which were not different from those described for other populations. The authors found that concomitant use of co-trimoxazole leads to a reduced formation rate (-51%) of hydroxyitraconazole.