PURPOSE: A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS: An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plasma concentration was measured by high-performance liquid chromatography (HPLC) assay, and a one-compartment model with first-order absorption was fitted to the data using NONMEM version V level 1.1. RESULTS: The mean peak and trough plasma concentration values of domperidone were, respectively, 25.3 +/- 20.5 ng/ml and 15.4 +/- 11.4 ng/ml (mean +/- standard deviation). The pharmacokinetic parameters (interindividual variability%) were clearance (Cl/F) = 0.92 L/h (51.6%), volume of distribution (Vd/F) = 0.405 L (68%), and absorption constant rate (Ka) = 0.0843 h(-1) (55.8%). The clearance is not lower than values reported in adults. No influence of covariates (postnatal age, prematurity, weight, gender) on domperidone pharmacokinetic parameters was found. CONCLUSION: This pilot study designed with a limited sampling strategy showed that domperidone plasma concentrations were consistent with those reported in adults, suggesting that domperidone dosage regimen currently used in preterm neonates is suitable.
PURPOSE: A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS: An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plasma concentration was measured by high-performance liquid chromatography (HPLC) assay, and a one-compartment model with first-order absorption was fitted to the data using NONMEM version V level 1.1. RESULTS: The mean peak and trough plasma concentration values of domperidone were, respectively, 25.3 +/- 20.5 ng/ml and 15.4 +/- 11.4 ng/ml (mean +/- standard deviation). The pharmacokinetic parameters (interindividual variability%) were clearance (Cl/F) = 0.92 L/h (51.6%), volume of distribution (Vd/F) = 0.405 L (68%), and absorption constant rate (Ka) = 0.0843 h(-1) (55.8%). The clearance is not lower than values reported in adults. No influence of covariates (postnatal age, prematurity, weight, gender) on domperidone pharmacokinetic parameters was found. CONCLUSION: This pilot study designed with a limited sampling strategy showed that domperidone plasma concentrations were consistent with those reported in adults, suggesting that domperidone dosage regimen currently used in preterm neonates is suitable.
Authors: W Meuldermans; R Hurkmans; E Swysen; J Hendrickx; M Michiels; W Lauwers; J Heykants Journal: Eur J Drug Metab Pharmacokinet Date: 1981 Impact factor: 2.441
Authors: Julie Autmizguine; Daniel K Benjamin; P Brian Smith; Mario Sampson; Philippe Ovetchkine; Michael Cohen-Wolkowiez; Kevin M Watt Journal: Curr Clin Pharmacol Date: 2014