Therapeutic drug monitoring of posaconazole in hematology adults under posaconazole prophylaxis: influence of food intake.

Posaconazole (PCZ) is given at 200 mg three times daily as a fungal prophylaxis in neutropenic hematologic malignancy patients. A relationship between exposure, plasma concentration, and efficacy is suggested. The objectives of this prospective study were to analyze the PCZ plasma concentration in hematology adults at high risk of developing invasive fungal infections (IFIs), and factors that could have an impact on the PCZ plasma concentration. PCZ plasma concentrations were measured after 2, 7, 10, 14, and 21 days of PCZ prophylaxis. Factors such as gender, age, body weight, posology, treatment duration, mucositis, proton pump inhibitor (PPI) use, and food intake were studied. Sixty-three patients were included, with a median age of 52 years (range 17-70) and a median weight of 75 kg (range 47-150). The median PCZ plasma concentration of the 63 patients ranged from 0.42 to 0.48 mg/L. At day 2, 30% of PCZ plasma concentration were under 0.35 mg/L, and at day 7, 74% were <0.70 mg/L. PCZ plasma concentrations were not affected by gender, age, body weight, or treatment duration. We found that food intake had a high influence on PCZ plasma concentrations (p = 0.0049). PCZ was well tolerated. One patient has developed a probable IFI, probably related to a low exposure to PCZ. PCZ therapeutic drug monitoring (TDM) is essential in order to early detect patients with low concentrations, to assess the etiology of such results, and to decide on the treatment strategy to apply.

Inherited long QT syndrome revealed by antifungals drug-drug interaction.

A 14-year-old Tahitian girl with acute myeloid leukaemia and a suspected mucormucosis infection was treated with intravenous voriconazole and caspofungin. Because of worsening of fungal infection, voriconazole was switched to posaconazole. During the switch, the patient presented with QT interval prolongation with 'torsades de pointes' and reversible cardiac arrest. Voriconazole plasma level measured 15 h after the last administration was 7 mg/L. Genotyping suggested that the patient was an extensive metabolizer with respect to CYP2C9 and CYP2C19. The association of antifungal agents with pro-arrhythmogenic drugs and other risk factors led to torsades de pointes and the revealing of inherited QT syndrome.

Monitoring ground water for pesticides in the U.S.A.

At least 17 pesticides have been found in ground water in a total of 23 states as a result of agricultural practice. These results have been obtained through three different types of monitoring studies: large-scale retrospective, small-scale retrospective, and small-scale prospective. The first two types of studies survey areas where the pesticide(s) in question has already been used. The third type of study is an intensive field study where the pesticide is applied and monitoring begins at time zero. Often, soil core data are at least as important as ground water data. The ability to draw meaningful conclusions from large-scale studies is greatly diminished unless the studies have a statistical, stratified design. The purpose of this paper is threefold: to describe the three study types; suggest guidelines for groundwater sampling, soil sampling and well construction; and update the data summary of pesticides in ground water from agricultural practice.