Therapeutic drug monitoring (TDM) of gentamicin in neonates is recommended for safe and effective dosing and is currently performed by plasma sampling, which is an invasive and painful procedure. In this study, feasibility of a non-invasive gentamicin TDM strategy using saliva was investigated.Methods: This was a multicentre, prospective, observational cohort study including 54 neonates. Any neonate treated with intravenous gentamicin was eligible for the study. Up to eight saliva samples were collected per patient at different time-points.Gentamicin levels in saliva were determined with liquid chromatography tandem mass-spectrometry (LC-MS/MS). A population pharmacokinetic (PK) model was developed using nonlinear mixed-effects modelling (NONMEM) to describe the relation between gentamicin concentrations in saliva and plasma. Monte Carlo simulations with a representative virtual cohort (n = 3000) were performed to evaluate the probability of target attainment with saliva versus plasma TDM.Results: Plasma PK was adequately described with an earlier published model. An additional saliva compartment describing the salivary gentamicin concentrations was appended to the model with first-order input (k 13 0.023 h À1 ) and first-order elimination (k 30 0.169 h À1 ). Inter-individual variability of k 30 was 38%. Postmenstrual age Amadou Samb and Matthijs Kruizinga contributed equally to this study.The authors confirm that the Principal Investigator for this paper is Timo R. de Haan and that he had direct clinical responsibility for patients.
Misuse of organophosphate insecticides, even in case of domestic application, can be life threatening. We report the case of siblings admitted with respiratory distress, pinpoint pupils and slurred speech. The symptoms appear after spraying the skin by insecticides. Plasma pseudocholinesterase level appeared to be very low, consistent with acute intoxication with organophosphate insecticide.Management of organophosphate poisoning consists of airway management, administration of oxygen and fluid, as well as atropine in increasing doses and pralidoxime. Decontamination of the patient's skin and the removal of the patient's clothes are mandatory in order to avoid recontamination of the patient as well as the surrounding healthcare personnel.Plasma pseudocholinesterase analysis is a cheap and an easy indicator for organophosphate insecticides intoxications and could be used for diagnosis and treatment monitoring.
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