Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants

AimThe therapeutic options available to treat neonatal pain are limited, and one alternative for nonopioid systemic treatment is paracetamol. However, pharmacokinetic data from prolonged administration of intravenous paracetamol in neonates are limited. The aim of this study was to present pharmacokinetics after multiple dose of intravenous paracetamol in very preterm infants of <32weeks' gestation. MethodsFifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. ResultsA two-compartment pharmacokinetic model gave the best fit for all individual patients and resulted in a predictable pharmacokinetic profile. The estimated pharmacokinetic population parameters were volume of distribution 0.7640.225L/kg, elimination rate constant (k(e)) 0.117 +/- 0.091/h and intercompartment rate constants k(12) 0.607 +/- 0.734/h and k(21) 1.105 +/- 0.762/h. ConclusionOur study found that multiple doses of intravenous paracetamol resulted in a predictable pharmacokinetic profile in very preterm infants. Increases in postmenstrual age and weight were associated with increased clearance. No evidence of hepatotoxicity was found

Necrotizing Enterocolitis, Gut Microbiota, and Brain Development:Role of the Brain-Gut Axis

Necrotizing enterocolitis (NEC) is a relatively common disease in very-low-birth-weight infants and is associated with high mortality and morbidity. In survivors, neurodevelopmental impairment is frequently seen. The exact etiology remains largely to be elucidated, but microbiota are considered to play a major role in the development of NEC. Furthermore, emerging evidence exists that the microbiota is also of importance in brain function and development. Therefore, microbiota characterization has not only potential as a diagnostic or even preventive tool to predict NEC, but may also serve as a biomarker to monitor and possibly even as a target to manipulate brain development. Analysis of fecal volatile organic compounds, which shape the volatile metabolome and reflect microbiota function and host interaction, has been shown to be of interest in the diagnosis of NEC and late-onset sepsis. In this review, we discuss evidence of the role of the complex interplay between microbiota, NEC, and brain development, including the brain-gut axis in preterm infants

Necrotizing enterocolitis, gut microbiota, and brain development:role of the brain-gut axis

\u3cp\u3eNecrotizing enterocolitis (NEC) is a relatively common disease in very-low-birth-weight infants and is associated with high mortality and morbidity. In survivors, neurodevelopmental impairment is frequently seen. The exact etiology remains largely to be elucidated, but microbiota are considered to play a major role in the development of NEC. Furthermore, emerging evidence exists that the microbiota is also of importance in brain function and development. Therefore, microbiota characterization has not only potential as a diagnostic or even preventive tool to predict NEC, but may also serve as a biomarker to monitor and possibly even as a target to manipulate brain development. Analysis of fecal volatile organic compounds, which shape the volatile metabolome and reflect microbiota function and host interaction, has been shown to be of interest in the diagnosis of NEC and late-onset sepsis. In this review, we discuss evidence of the role of the complex interplay between microbiota, NEC, and brain development, including the brain-gut axis in preterm infants.\u3c/p\u3