Population pharmacokinetics of caffeine in premature neonates (original) (raw)

Abstract

Objective: To determine population pharmacokinetic parameters of caeine in premature neonates. Methods: This population analysis was done using 145 serum concentration measurements gathered from 75 hospitalized patients during their routine clinical care. The data were analysed by use of NONMEM (mixed eects modelling) according to a one-compartment open model with either zero or ®rst-order absorption and ®rst-order elimination. The eect of a variety of developmental, demographic and clinical factors (gender, birth weight, current weight, gestational age, postnatal age, postconceptional age and concurrent treatment with phenobarbital and parenteral nutrition) on clearance and volume of distribution was investigated. Forward selection and backward elimination regression identi®ed signi®cant covariates. Results: The ®nal pharmacostatistical model with inuential covariates were as follows: clearance (ml á h )1 ) 5.81 á current weight (kg) + 1.22 á postnatal age (weeks), multiplied by 0.757 if gestational age £ 28 weeks and 0.836 if the current primary source of patients' nutrition is parenteral nutrition, and volume of distribution (ml) 911 á current weight (kg). The interindividual variability in clearance and the residual variability, expressed as coecients of variation, were 14.87% and 18.44%, respectively. Due to the lack of information on the data set we were unable to characterize the interindividual variability for volume of distribution. Conclusion: In this study, which involved on average only two serum concentrations of caeine per patient, the use of NONMEM gave us signi®cant and consistent information about the pharmacokinetic pro®le of caffeine when compared with available bibliographic information. Additionally, parenteral nutrition and low gestational age (£ 28 weeks) may even come to be considered as risk factors, and their presence may serve as an indicator of the need for periodic monitoring of caeine concentrations in premature infants.

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