RESUMEN
In order to evaluate dermal absorption during typical working conditions in family farming, the amount of dimethoate on clothing and in the stratum corneum (SC) was measured in three rural workers. This was achieved by using cotton patches on the worker's clothes and SC quantification by the tape stripping approach. To mimic the above study, an in vitro approach was performed using Franz cells by applying dimethoate (0.4 and 1.8⯵g) direct to pig skin or, on a section of cotton before contact with pig skin. The in vivo case results demonstrated the high levels and variability of agrochemicals to which these farmers are subjected, with the total potential dermal absorption between 0.87-2.85â¯mg/person/h and the estimated SC penetration factor (PF) between 0-54.0 and 0-28.9 % for the back of the neck and the arms respectively. This probably demonstrates the impact of correct protective clothing. For the in vitro study, the amount of pesticide retained in the SC was 52.63⯱â¯10.73and 135.15⯱â¯31.8â¯ng/cm2 after applying 0.4 and 1.8⯵g of pesticide directly on SC, and demonstrated close agreement with the in vivo approach. Further studies performed with this and other pesticides with different characteristics will contribute to the understanding of their transport through the skin.
Asunto(s)
Exposición Profesional/análisis , Plaguicidas/metabolismo , Absorción Cutánea , Agricultura , Humanos , Ropa de Protección , Piel/metabolismoRESUMEN
Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml-1 Intra- and interday precision and bias values were less than 14.87% (n = 9) and 9.81% (n = 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 = 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.