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1.
J Infect Chemother ; 26(1): 132-135, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31350185

RESUMO

Aspergillosis is a rare fungal infection in newborns, and its morbidity and mortality are high. Voriconazole (VRCZ) is the first-line antifungal agent for invasive Aspergillus infection, but little data is available about its pharmacokinetics in infants. We report a case of a premature infant who developed ventriculitis due to Aspergillus fumigatus and received combination antifungal therapy including VRCZ. ß-D glucan and Aspergillus antigen index were elevated in the cerebrospinal fluid (CSF). We titrated the dose of VRCZ by monitoring plasma and CSF concentrations. The CSF to plasma concentration ratio of VRCZ ranged from 0.47 to 1.36 (median 0.71). While VRCZ adequately penetrates the blood-brain barrier, its concentration is highly variable in infants.


Assuntos
Antifúngicos , Aspergillus fumigatus , Ventriculite Cerebral/tratamento farmacológico , Neuroaspergilose/tratamento farmacológico , Voriconazol , Antifúngicos/sangue , Antifúngicos/líquido cefalorraquidiano , Antifúngicos/uso terapêutico , Monitoramento de Medicamentos , Humanos , Recém-Nascido , Masculino , Voriconazol/sangue , Voriconazol/líquido cefalorraquidiano , Voriconazol/uso terapêutico
2.
J Pharmacol Exp Ther ; 365(2): 408-412, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29491040

RESUMO

Cerebral Scedosporium infections usually occur in lung transplant recipients as well as in immunocompetent patients in the context of near drowning. Voriconazole is the first-line treatment. The diffusion of voriconazole through the blood-brain barrier in the context of cerebral infection and cyclosporine administration is crucial and remains a matter of debate. To address this issue, the pharmacokinetics of voriconazole was assessed in the plasma, cerebrospinal fluid (CSF), and brain in an experimental model of cerebral scedosporiosis in rats receiving or not receiving cyclosporine. A single dose of voriconazole (30 mg/kg, i.v.) was administered to six groups of rats randomized according to the infection status and the cyclosporine dosing regimen (no cyclosporine, a single dose, or three doses; 15 mg/kg each). Voriconazole concentrations in plasma, CSF, and brain samples were quantified using ultra-performance liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography UV methods and were documented up to 48 hours after administration. Pharmacokinetic parameters were estimated using a noncompartmental approach. Voriconazole pharmacokinetic profiles were similar for plasma, CSF, and brain in all groups studied. The voriconazole Cmax and area under the curve (AUC) (AUC0 ≥ 48 hours) values were significantly higher in plasma than in CSF [CSF/plasma ratio, median (range) = 0.5 (0.39-0.55) for AUC0 ≥ 48 hours and 0.47 (0.35 and 0.75) for Cmax]. Cyclosporine administration was significantly associated with an increase in voriconazole exposure in the plasma, CSF, and brain. In the plasma, but not in the brain, an interaction between the infection and cyclosporine administration reduced the positive impact of cyclosporine on voriconazole exposure. Together, these results emphasize the impact of cyclosporine on brain voriconazole exposure.


Assuntos
Ciclosporina/farmacologia , Micoses/tratamento farmacológico , Voriconazol/farmacocinética , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Modelos Animais de Doenças , Masculino , Micoses/sangue , Micoses/líquido cefalorraquidiano , Micoses/metabolismo , Ratos , Ratos Sprague-Dawley , Scedosporium/fisiologia , Voriconazol/sangue , Voriconazol/líquido cefalorraquidiano , Voriconazol/uso terapêutico
3.
J Chemother ; 29(1): 42-44, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25748533

RESUMO

This case report indicates the usefulness of voriconazole for the treatment of central nervous system (CNS) aspergillosis, also in paediatrics. However, it also confirms the need for therapeutic drug monitoring (TDM), especially in younger children that may require very high dosages in order to achieve plasma and cerebrospinal fluid (CSF) therapeutic concentrations.


Assuntos
Antifúngicos/administração & dosagem , Neuroaspergilose/tratamento farmacológico , Voriconazol/administração & dosagem , Antifúngicos/líquido cefalorraquidiano , Antineoplásicos/uso terapêutico , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Neuroaspergilose/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Voriconazol/líquido cefalorraquidiano
4.
J Vet Pharmacol Ther ; 38(5): 451-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25691353

RESUMO

The goal of this project was to determine the pharmacokinetics of voriconazole and its concentration in cerebrospinal fluid (CSF), aqueous humor, and synovial fluid in five healthy dogs following once daily oral dose of 6 mg/kg for 2 weeks. Body fluid and plasma drug concentrations were determined by high-performance liquid chromatography (HPLC). Mild to moderate gastrointestinal adverse effects were seen. The mean AUC0-24 : minimum inhibitory concentration (MIC) ratio was 15.23 for a chosen MIC of 1 µg/mL, which is lower than the recommended target of 20-25 and also lower than previously reported in dogs, perhaps reflecting induction of metabolizing enzymes by multiple dosing. Voriconazole concentrations in the CSF, aqueous humor, and synovial fluid were only 13-30% the concurrent plasma concentration, which is lower than previously reported in other species. Results of this study suggest that twice daily, administration may be necessary to maintain therapeutic plasma concentrations in dogs but further studies are warranted.


Assuntos
Antifúngicos/farmacocinética , Voriconazol/farmacocinética , Administração Oral , Animais , Antifúngicos/administração & dosagem , Antifúngicos/análise , Antifúngicos/sangue , Antifúngicos/líquido cefalorraquidiano , Humor Aquoso/química , Cromatografia Líquida de Alta Pressão/veterinária , Cães , Feminino , Masculino , Testes de Sensibilidade Microbiana/veterinária , Líquido Sinovial/química , Voriconazol/administração & dosagem , Voriconazol/análise , Voriconazol/sangue , Voriconazol/líquido cefalorraquidiano
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